Hydrogels – Delivery Systems
Hydrogel-based matrices are used to release, in a controll manner, active ingredients. These systems can be “loaded” with specific molecules/microparticles that can be released more or less gradually (controlled release) depending on external stimuli (change of temperature, pH, ionic strength and so forth). The active ingredient release mechanism is based on the ability of these systems to adsorb/desorb great amount of water (or biological fluids), that produces at the same time the structural change of the polymer network that, in turns, affects the mobility of the active ingredient and therefore the release toward the external environment. The pharma sector uses this technology to produce tablets that, depending on the polymer employed, can be designed to release the drug in a controll manner in different zones of the gastrointestinal tract. The same type of use can be exploited by the food sector to produce nutraceuticals. The agro sector instead make use of this technology to produce prolonged/controlled release agrochemicals/fertilizers, in granulate form, to reduce the number of treatments.
The study and understanding of the main phenomena that influence the behavior of these systems is therefore vital for proper design, manufacturing and application of matrix-based.
Do you want to know more about hydrogel and active ingredient delivery mechanism? Read this.
Research lines
The TPP group deals with the study of systems based on hydrogels with a combined approach, analyzing experimental and modeling aspects, to identify, quantify, and manipulate the key parameters that affect their behavior. Our research can be summarized as:
Characterization of the behavior of systems based on hydrogels
- Analyses of the release of the active ingredient
- Analytical quantification
- Analyses of the swelling
- Gravimetric techniques, image analyses, texture analyses
- Analyses of the gel erosion
- Gravimetric techniques, analytical quantification
- Characterization of the sol-gel behavior in physical gels (i.e. HPMC)
- Mechanical and reological tests
Related publications:
2022
Piano, Raffaella De; Caccavo, Diego; Barba, Anna Angela; Lamberti, Gaetano
Anionic hydrogels: equilibrium behaviour modelling Proceedings Article
In: CHISA - Prague (Czech Republic), 2022.
@inproceedings{Piano}2022,
title = {Anionic hydrogels: equilibrium behaviour modelling},
author = {Raffaella {De Piano} and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti},
year = {2022},
date = {2022-08-23},
booktitle = {CHISA - Prague (Czech Republic)},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
2021
Yu, Xu-Dong; Li, Jia-Hui; Li, Heng; Huang, Ju; Caccavo, Diego; Lamberti, Gaetano; Chu, Li-Qiang
Gelation process of carboxymethyl chitosan-zinc supramolecular hydrogel studied with fluorescence imaging and mathematical modelling Journal Article
In: International Journal of Pharmaceutics, vol. 605, no. 120804, 2021, ISBN: 218995.
@article{Yu2021,
title = {Gelation process of carboxymethyl chitosan-zinc supramolecular hydrogel studied with fluorescence imaging and mathematical modelling},
author = {Xu-Dong Yu and Jia-Hui Li and Heng Li and Ju Huang and Diego Caccavo and Gaetano Lamberti and Li-Qiang Chu },
url = {https://www.sciencedirect.com/science/article/pii/S0378517321006098},
doi = {10.1016/j.ijpharm.2021.120804},
isbn = {218995},
year = {2021},
date = {2021-06-16},
journal = {International Journal of Pharmaceutics},
volume = {605},
number = {120804},
abstract = {Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72×10-6 cm2/s to 4.50×10-6 cm2/s. The gelation kinetics then is described with a “zero order” mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72×10-6 cm2/s to 4.50×10-6 cm2/s. The gelation kinetics then is described with a “zero order” mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel.2018
Caccavo, Diego; Vietri, Antonella; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Modeling the mechanics and the transport phenomena in hydrogels Book Chapter
In: Manca, Davide (Ed.): Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications, Chapter 12, 2018.
@inbook{Caccavo2018b,
title = {Modeling the mechanics and the transport phenomena in hydrogels},
author = {Diego Caccavo and Antonella Vietri and Gaetano Lamberti and Anna Angela Barba and Anette Larsson },
editor = {Davide Manca},
url = {https://www.sciencedirect.com/science/article/pii/B978044463964600012X},
doi = {10.1016/B978-0-444-63964-6.00012-X},
year = {2018},
date = {2018-07-18},
booktitle = {Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications},
chapter = {12},
abstract = {Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as\textemdashin principle\textemdashany other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as—in principle—any other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour Journal Article
In: Chemical Society Reviews, vol. 47, no. 7, pp. 2357-2373, 2018, ISSN: 0306-0012.
@article{Caccavo2018,
title = {Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://pubs.rsc.org/en/content/articlelanding/2018/cs/c7cs00638a#!divAbstract},
doi = {10.1039/C7CS00638A},
issn = {0306-0012},
year = {2018},
date = {2018-04-07},
journal = {Chemical Society Reviews},
volume = {47},
number = {7},
pages = {2357-2373},
abstract = {Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure\textendashproperty relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure–property relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.2017
Caccavo, Diego; Barba, Anna Angela; D'Amore, Matteo; Piano, Raffaella De; Lamberti, Gaetano; Rossi, Alessandra; Colombo, Paolo
Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix® Journal Article
In: European Journal of Pharmaceutics and Biopharmaceutics, vol. 121, pp. 24-31, 2017, ISSN: 0939-6411.
@article{Caccavo2017b,
title = {Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®},
author = {Diego Caccavo and Anna Angela Barba and Matteo D'Amore and Raffaella {De Piano} and Gaetano Lamberti and Alessandra Rossi and Paolo Colombo},
url = {http://www.sciencedirect.com/science/article/pii/S0939641117308366},
doi = {10.1016/j.ejpb.2017.08.016},
issn = {0939-6411},
year = {2017},
date = {2017-12-01},
journal = {European Journal of Pharmaceutics and Biopharmaceutics},
volume = {121},
pages = {24-31},
abstract = {The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Abrahmsén-Alami, Susanna; Viridén, Anna; Larsson, Anette
Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study Journal Article
In: International Journal of Pharmaceutics, vol. 528, no. 1-2, pp. 705-713, 2017, ISSN: 0378-5173.
@article{Larsson2017,
title = {Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study},
author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Susanna Abrahms\'{e}n-Alami and Anna Virid\'{e}n and Anette Larsson},
url = {http://www.sciencedirect.com/science/article/pii/S0378517317305720},
doi = {10.1016/j.ijpharm.2017.06.064},
issn = {0378-5173},
year = {2017},
date = {2017-08-07},
journal = {International Journal of Pharmaceutics},
volume = {528},
number = {1-2},
pages = {705-713},
abstract = {The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices.Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela
Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications Journal Article
In: Natural Product Communications, vol. 12, no. 6, pp. 867-871, 2017, ISSN: 1934-578X.
@article{NPC02,
title = {Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Annalisa Dalmoro and Anna Angela Barba},
url = {http://www.naturalproduct.us/index.asp
https://www.gruppotpp.it/wp-content/uploads/2017/06/Caccavo-et-al-NPC-126-867-871-2017-Abstract.pdf},
issn = {1934-578X},
year = {2017},
date = {2017-07-31},
journal = {Natural Product Communications},
volume = {12},
number = {6},
pages = {867-871},
abstract = {Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources.
In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources.
In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications.
Caccavo, Diego; Cascone, Sara; Poto, Serena; Lamberti, Gaetano; Barba, Anna Angela
Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests Journal Article
In: Carbohydrate Polymers, vol. 167, pp. 136–144, 2017.
@article{Caccavo2017b,
title = {Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests},
author = {Diego Caccavo and Sara Cascone and Serena Poto and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0144861717302837},
doi = {10.1016/j.carbpol.2017.03.027},
year = {2017},
date = {2017-07-01},
journal = {Carbohydrate Polymers},
volume = {167},
pages = {136\textendash144},
abstract = {Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior.Kazlauske, Jurgita; Cafaro, Maria Margherita; Caccavo, Diego; Marucci, Maria Grazia; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose Journal Article
In: International Journal of Pharmaceutics, vol. 528, no. 1-2, pp. 345-353, 2017, ISSN: 0378-5173.
@article{Kazlauske2017,
title = {Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose},
author = {Jurgita Kazlauske and Maria Margherita Cafaro and Diego Caccavo and Maria Grazia Marucci and Gaetano Lamberti and Anna Angela Barba and Anette Larsson},
url = {http://www.sciencedirect.com/science/article/pii/S0378517317304970},
doi = {10.1016/j.ijpharm.2017.05.073},
issn = {0378-5173},
year = {2017},
date = {2017-06-17},
journal = {International Journal of Pharmaceutics},
volume = {528},
number = {1-2},
pages = {345-353},
abstract = {The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate.Caccavo, Diego; Lamberti, Gaetano; Cafaro, Maria Margherita; Barba, Anna Angela; Kazlauske, Jurgita; Larsson, Anette
Mathematical modeling of the drug release from an ensemble of coated pellets Journal Article
In: British Journal of Pharmacology, vol. 174, no. 12, pp. 1797–1809 , 2017, ISBN: 1476-5381.
@article{Caccavo2017b,
title = {Mathematical modeling of the drug release from an ensemble of coated pellets},
author = {Diego Caccavo and Gaetano Lamberti and Maria Margherita Cafaro and Anna Angela Barba and Jurgita Kazlauske and Anette Larsson},
url = {http://onlinelibrary.wiley.com/doi/10.1111/bph.13776/abstract},
doi = {10.1111/bph.13776},
isbn = {1476-5381},
year = {2017},
date = {2017-04-22},
journal = {British Journal of Pharmacology},
volume = {174},
number = {12},
pages = {1797\textendash1809 },
abstract = {Background and Purpose
Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models.
Experimental approach
In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets.
Key Results
In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release.
Conclusions and Implications
The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background and Purpose
Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models.
Experimental approach
In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets.
Key Results
In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release.
Conclusions and Implications
The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.Dalmoro, Annalisa; Abrami, Michela; Galzerano, Barbara; Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Mario; Larobina, Domenico
Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests Journal Article
In: Current Drug Delivery, vol. 14, no. 2, pp. 216 - 223, 2017.
@article{Dalmoro2016b,
title = { Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests},
author = {Annalisa Dalmoro and Michela Abrami and Barbara Galzerano and Sabrina Bochicchio and Anna Angela Barba and Mario Grassi and Domenico Larobina},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/06.-Dalmoro-et-al-CDD-142-216-223-2017.pdf
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/216/
},
doi = {10.2174/1567201813666160721142202},
year = {2017},
date = {2017-02-08},
issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},
journal = {Current Drug Delivery},
volume = {14},
number = {2},
pages = {216 - 223},
abstract = {Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the “optimized composition”, namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.},
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Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the “optimized composition”, namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.2016
Lamberti, Gaetano; Barba, Anna Angela; Cascone, Sara; Dalmoro, Annalisa; Caccavo, Diego
An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications Book Chapter
In: Majee, Sutapa Biswas (Ed.): Emerging Concepts in Analysis and Applications of Hydrogels, Chapter 8, Intech, 2016, ISBN: 978-953-51-2510-5.
@inbook{Lamberti2016b,
title = {An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications},
author = {Gaetano Lamberti and Anna Angela Barba and Sara Cascone and Annalisa Dalmoro and Diego Caccavo},
editor = {Sutapa Biswas Majee},
url = {http://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-of-hydrogels/an-engineering-point-of-view-on-the-use-of-the-hydrogels-for-pharmaceutical-and-biomedical-applicati},
doi = {10.5772/64299 },
isbn = {978-953-51-2510-5},
year = {2016},
date = {2016-08-24},
booktitle = {Emerging Concepts in Analysis and Applications of Hydrogels},
publisher = {Intech},
chapter = {8},
abstract = {In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.},
keywords = {},
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In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Swellable Hydrogel-based Systems for Controlled Drug Delivery Book Chapter
In: Sezer, Ali Demir (Ed.): Smart Drug Delivery System, Chapter 10, Intech, 2016, ISBN: 978-953-51-2247-0.
@inbook{Caccavo2016b,
title = {Swellable Hydrogel-based Systems for Controlled Drug Delivery},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson},
editor = {Ali Demir Sezer},
url = {http://www.intechopen.com/books/smart-drug-delivery-system/swellable-hydrogel-based-systems-for-controlled-drug-delivery#exportas},
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isbn = {978-953-51-2247-0},
year = {2016},
date = {2016-02-10},
booktitle = {Smart Drug Delivery System},
publisher = {Intech},
chapter = {10},
abstract = {The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass\textendashrubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.},
keywords = {},
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The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass–rubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.Caccavo, Diego; Ström, Anna; Larsson, Anette; Lamberti, Gaetano
Modeling capillary formation in calcium and copper alginate gels Journal Article
In: Materials Science and Engineering: C, vol. 58, pp. 442–449, 2016, ISSN: 09284931.
@article{Caccavo2016,
title = {Modeling capillary formation in calcium and copper alginate gels},
author = { Diego Caccavo and Anna Str\"{o}m and Anette Larsson and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0928493115302940},
doi = {10.1016/j.msec.2015.08.040},
issn = {09284931},
year = {2016},
date = {2016-01-01},
journal = {Materials Science and Engineering: C},
volume = {58},
pages = {442--449},
abstract = {Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.},
keywords = {},
pubstate = {published},
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Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.2015
Caccavo, Diego; Lamberti, Gaetano; Cascone, Sara; Barba, Anna Angela; Larsson, Anette
Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment Journal Article
In: Carbohydrate Polymers, vol. 131, pp. 41–49, 2015, ISSN: 01448617.
@article{Caccavo2015b,
title = {Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment},
author = { Diego Caccavo and Gaetano Lamberti and Sara Cascone and Anna Angela Barba and Anette Larsson},
url = {http://www.sciencedirect.com/science/article/pii/S0144861715004476},
doi = {10.1016/j.carbpol.2015.05.041},
issn = {01448617},
year = {2015},
date = {2015-10-01},
journal = {Carbohydrate Polymers},
volume = {131},
pages = {41--49},
abstract = {The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.},
keywords = {},
pubstate = {published},
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}
The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.Abrahmsén-Alami, Susanna; Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Viridén, Anna; Larsson, Anette
Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach Journal Article
In: AstraZeneca Internal Journal, pp. 1-2, 2015.
@article{Abrahms\'{e}n-Alami2015,
title = {Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach},
author = {Susanna Abrahms\'{e}n-Alami and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Anna Virid\'{e}n and Anette Larsson},
year = {2015},
date = {2015-09-01},
journal = {AstraZeneca Internal Journal},
pages = {1-2},
abstract = {In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior \textendash as well as for the design \textendash of the tablets based on hydrogels.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior – as well as for the design – of the tablets based on hydrogels.Caccavo, Diego; Apicella, Pietro; Cascone, Sara; Dalmoro, Annalisa; Lamberti, Gaetano; Barba, Anna Angela
Hydrogels-based systems for controlled release in agricultural applications Proceedings Article
In: 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015.
@inproceedings{Caccavo2015b,
title = {Hydrogels-based systems for controlled release in agricultural applications},
author = {Diego Caccavo and Pietro Apicella and Sara Cascone and Annalisa Dalmoro and Gaetano Lamberti and Anna Angela Barba },
year = {2015},
date = {2015-07-26},
booktitle = {42nd Annual Meeting \& Exposition of the Controlled Release Society},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Hydrogel-Based CRSs Analyses: Testing And Modeling Proceedings Article
In: 1st International Congress of Controlled Release Society - Greek Local Chapter, pp. 1–1, 1st International Congress of Controlled Release Society, Athens (Greece), 2015.
@inproceedings{caccavo2015b,
title = {Hydrogel-Based CRSs Analyses: Testing And Modeling},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
year = {2015},
date = {2015-05-01},
booktitle = {1st International Congress of Controlled Release Society - Greek Local Chapter},
pages = {1--1},
publisher = {1st International Congress of Controlled Release Society},
address = {Athens (Greece)},
keywords = {},
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Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Controlled drug release from hydrogel-based matrices: Experiments and modeling. Journal Article
In: International journal of pharmaceutics, vol. 486, no. 1-2, pp. 144–152, 2015, ISSN: 1873-3476.
@article{Caccavo2015a,
title = {Controlled drug release from hydrogel-based matrices: Experiments and modeling.},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0378517315002707},
doi = {10.1016/j.ijpharm.2015.03.054},
issn = {1873-3476},
year = {2015},
date = {2015-03-01},
journal = {International journal of pharmaceutics},
volume = {486},
number = {1-2},
pages = {144--152},
abstract = {Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.Caccavo, Diego; Cascone, Sara; Amoroso, Maria Chiara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela
Hydrogel-based Granular Phytostrengtheners for Prolonged Release: Production and Characterization Journal Article
In: Chemical Engineering Transaction, vol. 44, pp. 235–240, 2015.
@article{Caccavo2015,
title = {Hydrogel-based Granular Phytostrengtheners for Prolonged Release: Production and Characterization},
author = { Diego Caccavo and Sara Cascone and Maria Chiara Amoroso and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.aidic.it/cet/15/44/040.pdf},
doi = {10.3303/CET1544040},
year = {2015},
date = {2015-01-01},
journal = {Chemical Engineering Transaction},
volume = {44},
pages = {235--240},
abstract = {Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are the decrease of the dosages number together with the increase of the active substance availability within the soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the effectiveness of the granulation process and the good flowability of the granules, highly desirable features for the product handling and commercialization.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are the decrease of the dosages number together with the increase of the active substance availability within the soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the effectiveness of the granulation process and the good flowability of the granules, highly desirable features for the product handling and commercialization.2014
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications Proceedings Article
In: Proceedings of CHISA 2014, pp. 1–1, CHISA 2014, Prague, Czech Republic, 2014.
@inproceedings{d.2014,
title = {Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
year = {2014},
date = {2014-08-01},
booktitle = {Proceedings of CHISA 2014},
pages = {1--1},
publisher = {CHISA 2014},
address = {Prague, Czech Republic},
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Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela
Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis Journal Article
In: Carbohydrate Polymers, vol. 103, pp. 348–354, 2014, ISSN: 01448617.
@article{Cascone2014,
title = {Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis},
author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0144861713012757},
doi = {10.1016/j.carbpol.2013.12.060},
issn = {01448617},
year = {2014},
date = {2014-03-01},
journal = {Carbohydrate Polymers},
volume = {103},
pages = {348--354},
abstract = {The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force\textendashpenetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force–penetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.2013
Lamberti, Gaetano; Cascone, Sara; Cafaro, Maria Margherita; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela
Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis. Journal Article
In: Carbohydrate polymers, vol. 92, no. 1, pp. 765–8, 2013, ISSN: 1879-1344.
@article{Lamberti2013a,
title = {Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis.},
author = { Gaetano Lamberti and Sara Cascone and Maria Margherita Cafaro and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0144861712010193},
doi = {10.1016/j.carbpol.2012.10.003},
issn = {1879-1344},
year = {2013},
date = {2013-01-01},
journal = {Carbohydrate polymers},
volume = {92},
number = {1},
pages = {765--8},
abstract = {In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.2012
Dalmoro, Annalisa; Barba, Anna Angela; Lamberti, Gaetano; Grassi, Mario; D'Amore, Matteo
Pharmaceutical applications of biocompatible polymer blends containing sodium alginate Journal Article
In: Advances in Polymer Technology, vol. 31, no. 3, pp. 219–230, 2012, ISSN: 07306679.
@article{Dalmoro2012a,
title = {Pharmaceutical applications of biocompatible polymer blends containing sodium alginate},
author = { Annalisa Dalmoro and Anna Angela Barba and Gaetano Lamberti and Mario Grassi and Matteo D'Amore},
url = {http://doi.wiley.com/10.1002/adv.21276},
doi = {10.1002/adv.21276},
issn = {07306679},
year = {2012},
date = {2012-09-01},
journal = {Advances in Polymer Technology},
volume = {31},
number = {3},
pages = {219--230},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
abstract = {Biocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shell\textendashcore particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures.},
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}
Biocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shell–core particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures.Lamberti, Gaetano; Cascone, Sara; Titomanlio, Giuseppe; Barba, Anna Angela
Controlled Release of Drugs From Hydrogel Based Matrices Systems: Experiments and Modeling Journal Article
In: Chemical and Biochemical Engineering Quarterly, vol. 26, no. 4, pp. 321–330, 2012, ISSN: 0352-9568.
@article{Lamberti2012c,
title = {Controlled Release of Drugs From Hydrogel Based Matrices Systems: Experiments and Modeling},
author = { Gaetano Lamberti and Sara Cascone and Giuseppe Titomanlio and Anna Angela Barba},
issn = {0352-9568},
year = {2012},
date = {2012-01-01},
journal = {Chemical and Biochemical Engineering Quarterly},
volume = {26},
number = {4},
pages = {321--330},
publisher = {Hrvatsko dru\v{s}tvo kemijskih in\v{z}enjera i tehnologa},
abstract = {Hydrogels are materials largely used in the formulation of pharmaceuticals since, in principle, they could produce a release system of zero-order kinetics, which is of great therapeutic interest. In this paper, a model was proposed for the description of the main transport phenomena involved in the drug release process from hydrogel matrices (water diffusion, polymer swelling, drug diffusion and polymer dissolution); the model predictions are successfully compared with a large set of experimental data, obtained working with matrices systems based on HPMC (Hydroxy Propyl Methyl Cellulose). The proposed model was found able to reproduce main features of the observed phenomena, it can thus be adopted for prediction of the performances of drug release systems from hydrogel matrices.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels are materials largely used in the formulation of pharmaceuticals since, in principle, they could produce a release system of zero-order kinetics, which is of great therapeutic interest. In this paper, a model was proposed for the description of the main transport phenomena involved in the drug release process from hydrogel matrices (water diffusion, polymer swelling, drug diffusion and polymer dissolution); the model predictions are successfully compared with a large set of experimental data, obtained working with matrices systems based on HPMC (Hydroxy Propyl Methyl Cellulose). The proposed model was found able to reproduce main features of the observed phenomena, it can thus be adopted for prediction of the performances of drug release systems from hydrogel matrices.2010
Barba, Anna Angela; D'Amore, Matteo; Cascone, Sara; Lamberti, Gaetano; Rabbia, Luca; Titomanlio, Giuseppe; Grassi, Mario; Grassi, Gabriele
Pluronic/alginate gels in drug eluting stents preparation Proceedings Article
In: Proceedings on CD-ROM of CHISA 2010 - ECCE 7, pp. 1–3, Chisa 2010, Praha, Czech Republic, 2010.
@inproceedings{a.a.2010,
title = {Pluronic/alginate gels in drug eluting stents preparation},
author = { Anna Angela Barba and Matteo D'Amore and Sara Cascone and Gaetano Lamberti and Luca Rabbia and Giuseppe Titomanlio and Mario Grassi and Gabriele Grassi},
year = {2010},
date = {2010-08-01},
booktitle = {Proceedings on CD-ROM of CHISA 2010 - ECCE 7},
pages = {1--3},
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Barba, Anna Angela; D'Amore, Matteo; Rabbia, Luca; Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; Grassi, Mario; Grassi, Gabriele
Gelification of polymer blends for coating of eluting stents Proceedings Article
In: Proceedings of 7th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, pp. 1–2, xxxx, Valletta (Malta), 2010, (Proc. su CD ROM).
@inproceedings{a.2010-1,
title = {Gelification of polymer blends for coating of eluting stents},
author = { Anna Angela Barba and Matteo D'Amore and Luca Rabbia and Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Mario Grassi and Gabriele Grassi},
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2009
Barba, Anna Angela; D'Amore, Matteo; Cascone, Sara; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe
On the behavior of HPMC/Theophylline matrices for controlled drug delivery Journal Article
In: Journal of Pharmaceutical Sciences, vol. 98, no. 11, pp. 4100–4110, 2009, ISSN: 00223549.
@article{Barba2009h,
title = {On the behavior of HPMC/Theophylline matrices for controlled drug delivery},
author = { Anna Angela Barba and Matteo D'Amore and Sara Cascone and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://doi.wiley.com/10.1002/jps.21701},
doi = {10.1002/jps.21701},
issn = {00223549},
year = {2009},
date = {2009-11-01},
journal = {Journal of Pharmaceutical Sciences},
volume = {98},
number = {11},
pages = {4100--4110},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
abstract = {Design of systems for oral controlled release of drug could take advantages from the knowledge of which phenomena take place. In this work matrices obtained by powders compression (50:50, hydroxypropyl methylcellulose, a swelling hydrogel, and theophylline, a model drug) were immersed in water at 37 degrees C, allowing the water uptake and the drug release by lateral surface, confining the cylindrical matrices between glass slides. The tablets, after given immersion times, were withdrawn, cut in several annuli, and subsequently analyzed for the drug and the water concentration radial profiles. The data confirmed the pseudo-diffusive nature of the process, allowing to give a deep insight into the drug release process from swellable hydrogel matrices. In particular, it was confirmed the presence of nonhomogeneous gel layer, rich in water and poor in drug, with a profile of drug concentration which agrees well with a pseudo-diffusion phenomenon.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Design of systems for oral controlled release of drug could take advantages from the knowledge of which phenomena take place. In this work matrices obtained by powders compression (50:50, hydroxypropyl methylcellulose, a swelling hydrogel, and theophylline, a model drug) were immersed in water at 37 degrees C, allowing the water uptake and the drug release by lateral surface, confining the cylindrical matrices between glass slides. The tablets, after given immersion times, were withdrawn, cut in several annuli, and subsequently analyzed for the drug and the water concentration radial profiles. The data confirmed the pseudo-diffusive nature of the process, allowing to give a deep insight into the drug release process from swellable hydrogel matrices. In particular, it was confirmed the presence of nonhomogeneous gel layer, rich in water and poor in drug, with a profile of drug concentration which agrees well with a pseudo-diffusion phenomenon.Barba, Anna Angela; D'Amore, Matteo; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe
Swelling of cellulose derivative (HPMC) matrix systems for drug delivery Journal Article
In: Carbohydrate Polymers, vol. 78, no. 3, pp. 469–474, 2009, ISSN: 01448617.
@article{Barba2009f,
title = {Swelling of cellulose derivative (HPMC) matrix systems for drug delivery},
author = { Anna Angela Barba and Matteo D'Amore and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S0144861709002707},
doi = {10.1016/j.carbpol.2009.05.001},
issn = {01448617},
year = {2009},
date = {2009-10-01},
journal = {Carbohydrate Polymers},
volume = {78},
number = {3},
pages = {469--474},
abstract = {The water swellable hydrogels are commonly used in the production of solid pharmaceutical dosage systems for oral administration (matrices). Their use allows to obtain the controlled drug release. The key role is played by the transport phenomena which take place: water up-take, gel swelling and erosion, increase in diffusivity due to hydration. Thus, knowledge of these phenomena is fundamental in designing and realizing the pharmaceutical systems. In this work, tablets made of pure hydrogel, HydroxyPropyl-MethylCellulose (HPMC), were produced and immersed in a thermostatic bath filled with stirred distilled water (37°C). The water up-take was allowed only by radial direction (from the lateral surface) by confining the tablet between two glass slides. Two distinct methods, an optical technique already described in a previous work, and a gravimetric procedure described here, were applied to measure the water concentration profiles along the radial direction in the tablets. The data obtained were used both to clarify the nature of the transport phenomena involved, and to perform a better tuning of a mathematical model previously proposed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The water swellable hydrogels are commonly used in the production of solid pharmaceutical dosage systems for oral administration (matrices). Their use allows to obtain the controlled drug release. The key role is played by the transport phenomena which take place: water up-take, gel swelling and erosion, increase in diffusivity due to hydration. Thus, knowledge of these phenomena is fundamental in designing and realizing the pharmaceutical systems. In this work, tablets made of pure hydrogel, HydroxyPropyl-MethylCellulose (HPMC), were produced and immersed in a thermostatic bath filled with stirred distilled water (37°C). The water up-take was allowed only by radial direction (from the lateral surface) by confining the tablet between two glass slides. Two distinct methods, an optical technique already described in a previous work, and a gravimetric procedure described here, were applied to measure the water concentration profiles along the radial direction in the tablets. The data obtained were used both to clarify the nature of the transport phenomena involved, and to perform a better tuning of a mathematical model previously proposed.Barba, Anna Angela; D'Amore, Matteo; Grassi, Mario; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe
Investigation of Pluronic© F127-Water solutions phase transitions by DSC and dielectric spectroscopy Journal Article
In: Journal of Applied Polymer Science, vol. 114, no. 2, pp. 688–695, 2009, ISSN: 00218995.
@article{Barba2009e,
title = {Investigation of Pluronic© F127-Water solutions phase transitions by DSC and dielectric spectroscopy},
author = { Anna Angela Barba and Matteo D'Amore and Mario Grassi and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://doi.wiley.com/10.1002/app.30586},
doi = {10.1002/app.30586},
issn = {00218995},
year = {2009},
date = {2009-10-01},
journal = {Journal of Applied Polymer Science},
volume = {114},
number = {2},
pages = {688--695},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
abstract = {The water solutions of the block copolymers PEOn-PPOm-PEOn, known as pluronics, show a complex thermal behavior, since they are liquid at low temperature (5°C), and they can give soft gel when heated at body temperature (37°C). These properties are of great interest in biomedical applications. To properly design these applications, a prerequisite is the knowledge of the thermodynamics\textemdashhow much\textemdashand of the kinetics\textemdashhow fast\textemdashwith which these transformations take place. In this work, solutions of F127 (the copolymer for which n = 100 and m = 65) were studied by varying the concentration and the temperature and analyzing their behavior when heated under several heating rates. The studies were performed by differential scanning calorimetry (DCS) and dielectric spectroscopy. The investigations carried out under equilibrium conditions allowed us to determine the thermodynamics of the phase transitions, whereas the investigations carried out under varying conditions allowed us to quantify the kinetics of the phase transitions. Empirical models were also proposed to describe both the thermodynamics and the kinetics observed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009},
keywords = {},
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}
The water solutions of the block copolymers PEOn-PPOm-PEOn, known as pluronics, show a complex thermal behavior, since they are liquid at low temperature (5°C), and they can give soft gel when heated at body temperature (37°C). These properties are of great interest in biomedical applications. To properly design these applications, a prerequisite is the knowledge of the thermodynamics—how much—and of the kinetics—how fast—with which these transformations take place. In this work, solutions of F127 (the copolymer for which n = 100 and m = 65) were studied by varying the concentration and the temperature and analyzing their behavior when heated under several heating rates. The studies were performed by differential scanning calorimetry (DCS) and dielectric spectroscopy. The investigations carried out under equilibrium conditions allowed us to determine the thermodynamics of the phase transitions, whereas the investigations carried out under varying conditions allowed us to quantify the kinetics of the phase transitions. Empirical models were also proposed to describe both the thermodynamics and the kinetics observed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009Barba, Anna Angela; Chirico, Serafina; Dalmoro, Annalisa; Galzerano, Barbara; Lamberti, Gaetano
Water and drug mass fraction profiles in HPMC/TP matrices Proceedings Article
In: Proceedings of CRS36, pp. 1–4, Copenhagen, Danimarca, 2009.
@inproceedings{barba2009-3,
title = {Water and drug mass fraction profiles in HPMC/TP matrices},
author = { Anna Angela Barba and Serafina Chirico and Annalisa Dalmoro and Barbara Galzerano and Gaetano Lamberti},
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Barba, Anna Angela; Chirico, Serafina; Dalmoro, Annalisa; Lamberti, Gaetano
Simultaneous measurement of theophylline and cellulose acetate phthalate in phosphate buffer by UV analysis Journal Article
In: Can J Anal Sci Spectros, vol. 53, no. 6, pp. 249–253, 2009.
@article{Barba2009a,
title = {Simultaneous measurement of theophylline and cellulose acetate phthalate in phosphate buffer by UV analysis},
author = { Anna Angela Barba and Serafina Chirico and Annalisa Dalmoro and Gaetano Lamberti},
year = {2009},
date = {2009-01-01},
journal = {Can J Anal Sci Spectros},
volume = {53},
number = {6},
pages = {249--253},
abstract = {The oral administration of pH-sensitive drugs requires protecting the drug molecules from the acidic pH in the stomach: the simplest way is to use polymers as coating, especially polymers which are insoluble at low pH (in the stomach) and soluble under neutral conditions (in the intestine). The Cellulose Acetate Phosphate, CAP, is one of these polymers, and it is one of the most used coating polymers. Studies related to the behavior of such pharmaceutical systems require fast and accurate methods to assay the released drug concentration in dissolution medium. However, both the drug and the coating polymer are present in the dissolution bulk with unknown concentration, and they can interfere each other in assaying. In this communication, a simple method to assay, by UV analysis, Theophylline (TP) and Cellulose Acetate Phosphate concentrations in a dissolution medium, phosphate buffer pH 7.0 (BP), is proposed and validated.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The oral administration of pH-sensitive drugs requires protecting the drug molecules from the acidic pH in the stomach: the simplest way is to use polymers as coating, especially polymers which are insoluble at low pH (in the stomach) and soluble under neutral conditions (in the intestine). The Cellulose Acetate Phosphate, CAP, is one of these polymers, and it is one of the most used coating polymers. Studies related to the behavior of such pharmaceutical systems require fast and accurate methods to assay the released drug concentration in dissolution medium. However, both the drug and the coating polymer are present in the dissolution bulk with unknown concentration, and they can interfere each other in assaying. In this communication, a simple method to assay, by UV analysis, Theophylline (TP) and Cellulose Acetate Phosphate concentrations in a dissolution medium, phosphate buffer pH 7.0 (BP), is proposed and validated.Barba, Anna Angela; Lamberti, Gaetano
Verso un rilascio intelligente Journal Article
In: NCF-Notiziario Chimico Farmaceutico, vol. 48, no. 1, pp. 68–71, 2009, ISSN: 0393-3733.
@article{Barba2009b,
title = {Verso un rilascio intelligente},
author = { Anna Angela Barba and Gaetano Lamberti},
issn = {0393-3733},
year = {2009},
date = {2009-01-01},
journal = {NCF-Notiziario Chimico Farmaceutico},
volume = {48},
number = {1},
pages = {68--71},
abstract = {L’efficacia di una terapia farmacologica dipende molto dal profi lo di rilascio del principio attivo dalla forma farmaceutica selezionata. In riferimento alla via di somministrazione orale, comprendere i fenomeni che si verificano dopo l’ingestione di una compressa \'{e} un passaggio fondamentale per poter ottimizzare le formulazioni e le tecniche di preparazione. Investigare tali fenomeni \'{e} uno degli scopi della nostra ricerca, e nell’articolo sono presentati e discussi alcuni risultati selezionati.},
keywords = {},
pubstate = {published},
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L’efficacia di una terapia farmacologica dipende molto dal profi lo di rilascio del principio attivo dalla forma farmaceutica selezionata. In riferimento alla via di somministrazione orale, comprendere i fenomeni che si verificano dopo l’ingestione di una compressa é un passaggio fondamentale per poter ottimizzare le formulazioni e le tecniche di preparazione. Investigare tali fenomeni é uno degli scopi della nostra ricerca, e nell’articolo sono presentati e discussi alcuni risultati selezionati.2008
Barba, Anna Angela; Chirico, Serafina; D'Amore, Matteo; Lamberti, Gaetano; Titomanlio, Giuseppe
On the release of active molecules from hydrogels based tablets Proceedings Article
In: pp. 501, Salerno, Italia, 2008.
@inproceedings{barba2008-7,
title = {On the release of active molecules from hydrogels based tablets},
author = { Anna Angela Barba and Serafina Chirico and Matteo D'Amore and Gaetano Lamberti and Giuseppe Titomanlio},
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date = {2008-06-01},
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Barba, Anna Angela; Chirico, Serafina; D'Amore, Matteo; Lamberti, Gaetano; LANZA, R. F; Titomanlio, Giuseppe
Transport phenomena in HPMC based tablets containing theophylline as drug Proceedings Article
In: Proceedings of 6th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, pp. 1–4, Barcelona, Spain, 2008.
@inproceedings{barba2008-6,
title = {Transport phenomena in HPMC based tablets containing theophylline as drug},
author = { Anna Angela Barba and Serafina Chirico and Matteo D'Amore and Gaetano Lamberti and R.F LANZA and Giuseppe Titomanlio},
year = {2008},
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2007
Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
Analysis and modeling of Diclofenac Sodium release kinetics from HPMC tablets Proceedings Article
In: Proceedings of European Congress of Chemical Engineering (ECCE-6), pp. 253–254, Copenhagen, 2007.
@inproceedings{barba2007,
title = {Analysis and modeling of Diclofenac Sodium release kinetics from HPMC tablets},
author = { Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
year = {2007},
date = {2007-09-01},
booktitle = {Proceedings of European Congress of Chemical Engineering (ECCE-6)},
pages = {253--254},
address = {Copenhagen},
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Chirico, Serafina; Lamberti, Gaetano; NUNZIATA, V; Titomanlio, Giuseppe
Analysis and modeling of radial water up-take in pure HPMC tablets Proceedings Article
In: Proceedings of European Congress of Chemical Engineering (ECCE-6), pp. 251–252, Copenhagen, 2007.
@inproceedings{chirico2007b,
title = {Analysis and modeling of radial water up-take in pure HPMC tablets},
author = { Serafina Chirico and Gaetano Lamberti and V NUNZIATA and Giuseppe Titomanlio},
year = {2007},
date = {2007-09-01},
booktitle = {Proceedings of European Congress of Chemical Engineering (ECCE-6)},
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Chirico, Serafina; Dalmoro, Annalisa; Lamberti, Gaetano; Russo, Giuseppina; Titomanlio, Giuseppe
Analysis and modeling of swelling and erosion behavior for pure HPMC tablet Journal Article
In: Journal of Controlled Release, vol. 122, no. 2, pp. 181–188, 2007, ISSN: 01683659.
@article{Chirico2007,
title = {Analysis and modeling of swelling and erosion behavior for pure HPMC tablet},
author = { Serafina Chirico and Annalisa Dalmoro and Gaetano Lamberti and Giuseppina Russo and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S0168365907003215},
doi = {10.1016/j.jconrel.2007.07.001},
issn = {01683659},
year = {2007},
date = {2007-09-01},
journal = {Journal of Controlled Release},
volume = {122},
number = {2},
pages = {181--188},
abstract = {This work is focused on the transport phenomena which take place during immersion in water of pure hydroxypropylmethylcellulose tablets. The water uptake, the swelling and the erosion during immersion were investigated in drug-free systems, as a preliminary task before to undertake the study of drug-loaded ones. The tablets, obtained by powder compression, were confined between glass slabs to allow water uptake only by lateral surface and then immersed in distilled water at 37 °C, with simultaneous video-recording. By image analysis the normalized light intensity profiles were obtained and taken as a measure of the water mass fraction. The time evolutions of the total tablet mass, of the water mass and of the erosion radius were measured, too. Thus a novel method to measure polymer and water masses during hydration was pointed out. Then, a model consisting in the transient mass balance, accounting for water diffusion, diffusivity change due to hydration, swelling and erosion, was found able to reproduce all experimental data. Even if the model was already used in literature, the novelty of our approach is to compare model predictions with a complete set of experimental data, confirming that the main phenomena were correctly identified and described.},
keywords = {},
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This work is focused on the transport phenomena which take place during immersion in water of pure hydroxypropylmethylcellulose tablets. The water uptake, the swelling and the erosion during immersion were investigated in drug-free systems, as a preliminary task before to undertake the study of drug-loaded ones. The tablets, obtained by powder compression, were confined between glass slabs to allow water uptake only by lateral surface and then immersed in distilled water at 37 °C, with simultaneous video-recording. By image analysis the normalized light intensity profiles were obtained and taken as a measure of the water mass fraction. The time evolutions of the total tablet mass, of the water mass and of the erosion radius were measured, too. Thus a novel method to measure polymer and water masses during hydration was pointed out. Then, a model consisting in the transient mass balance, accounting for water diffusion, diffusivity change due to hydration, swelling and erosion, was found able to reproduce all experimental data. Even if the model was already used in literature, the novelty of our approach is to compare model predictions with a complete set of experimental data, confirming that the main phenomena were correctly identified and described.Cascone, Sara; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe
Water and theopylline transport phenomena within HPMC based tablets Proceedings Article
In: Proceedings of Innovation in Drug Delivery, pp. 1–2, Napoli, 2007.
@inproceedings{cascone2007-1,
title = {Water and theopylline transport phenomena within HPMC based tablets},
author = { Sara Cascone and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},
year = {2007},
date = {2007-09-01},
booktitle = {Proceedings of Innovation in Drug Delivery},
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2006
Lamberti, Gaetano; Chirico, Serafina; Titomanlio, Giuseppe
Analysis of the transport phenomena in swelling devices for controlled release of drug Proceedings Article
In: pp. x, Praha, Czech Republic, 2006.
@inproceedings{lamberti2006,
title = {Analysis of the transport phenomena in swelling devices for controlled release of drug},
author = { Gaetano Lamberti and Serafina Chirico and Giuseppe Titomanlio},
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Chirico, Serafina; Lamberti, Gaetano; Russo, Giuseppina; Titomanlio, Giuseppe
Swelling and erosion kinetics of HPMC based system for controlled drug release Proceedings Article
In: pp. x, Ischia (NA), 2006.
@inproceedings{chirico2006-1,
title = {Swelling and erosion kinetics of HPMC based system for controlled drug release},
author = { Serafina Chirico and Gaetano Lamberti and Giuseppina Russo and Giuseppe Titomanlio},
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0000
CREVATI, A; FERUGLIO, L; PERIN, D; Grassi, Gabriele; LAPASIN, Romano; Lamberti, Gaetano; Grassi, Mario
Gel di alginato-pluronico per il rilascio di agenti antiproliferativi Proceedings Article
In: pp. 99–104, Crotone, Italia, 0000.
@inproceedings{crevati2008,
title = {Gel di alginato-pluronico per il rilascio di agenti antiproliferativi},
author = { A CREVATI and L FERUGLIO and D PERIN and Gabriele Grassi and Romano LAPASIN and Gaetano Lamberti and Mario Grassi},
pages = {99--104},
address = {Crotone, Italia},
keywords = {},
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Barba, Anna Angela; Chirico, Serafina; D'Amore, Matteo; Lamberti, Gaetano; Titomanlio, Giuseppe
Hydration, swelling , erosion and drug release from HPMC and HPMC/TP Proceedings Article
In: pp. 61–64, Piano di Sorrento (NA), Italia, 0000.
@inproceedings{barba2008-4,
title = {Hydration, swelling , erosion and drug release from HPMC and HPMC/TP},
author = { Anna Angela Barba and Serafina Chirico and Matteo D'Amore and Gaetano Lamberti and Giuseppe Titomanlio},
pages = {61--64},
address = {Piano di Sorrento (NA), Italia},
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Barba, Anna Angela; D'Amore, Matteo; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe
Sul rilascio di molecole attive da compresse basate su idrogeli Proceedings Article
In: pp. 117–122, Crotone, Italia, 0000.
@inproceedings{barba2008-3,
title = {Sul rilascio di molecole attive da compresse basate su idrogeli},
author = { Anna Angela Barba and Matteo D'Amore and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},
pages = {117--122},
address = {Crotone, Italia},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Chirico, Serafina; Dalmoro, Annalisa; Lamberti, Gaetano; Russo, Giuseppina; Titomanlio, Giuseppe
Radial water up-take in pure HPMC tablet: analysis and model prediction Proceedings Article
In: Proceedings of Pharmaceutical Science World Congress, pp. 1–4, Amsterdam, 0000.
@inproceedings{chirico2007-1,
title = {Radial water up-take in pure HPMC tablet: analysis and model prediction},
author = { Serafina Chirico and Annalisa Dalmoro and Gaetano Lamberti and Giuseppina Russo and Giuseppe Titomanlio},
booktitle = {Proceedings of Pharmaceutical Science World Congress},
pages = {1--4},
address = {Amsterdam},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
Analysis of Mass Transfer during Controlled Release of Diclofenac from Commercial Tablets Proceedings Article
In: pp. x, Vienna (Austria), 0000.
@inproceedings{barba2006,
title = {Analysis of Mass Transfer during Controlled Release of Diclofenac from Commercial Tablets},
author = { Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
pages = {x},
address = {Vienna (Austria)},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Mathematical Modeling
- Description of the release with semi-empirical equations
- Mechanistic modeling of the hydrogel-based delivery systems:
- Finite Element Analysis (FEM)
- Active ingredient release
- Water adsorption
- System deformation
- Polymer erosion
- System mechanics
- Multiphasic approach
- Monophasic approach
- Finite Element Analysis (FEM)
Related publications:
Read More
2022
Piano, Raffaella De; Caccavo, Diego; Barba, Anna Angela; Lamberti, Gaetano
Anionic hydrogels: equilibrium behaviour modelling Proceedings Article
In: CHISA - Prague (Czech Republic), 2022.
@inproceedings{Piano}2022,
title = {Anionic hydrogels: equilibrium behaviour modelling},
author = {Raffaella {De Piano} and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti},
year = {2022},
date = {2022-08-23},
booktitle = {CHISA - Prague (Czech Republic)},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
2021
Yu, Xu-Dong; Li, Jia-Hui; Li, Heng; Huang, Ju; Caccavo, Diego; Lamberti, Gaetano; Chu, Li-Qiang
Gelation process of carboxymethyl chitosan-zinc supramolecular hydrogel studied with fluorescence imaging and mathematical modelling Journal Article
In: International Journal of Pharmaceutics, vol. 605, no. 120804, 2021, ISBN: 218995.
@article{Yu2021,
title = {Gelation process of carboxymethyl chitosan-zinc supramolecular hydrogel studied with fluorescence imaging and mathematical modelling},
author = {Xu-Dong Yu and Jia-Hui Li and Heng Li and Ju Huang and Diego Caccavo and Gaetano Lamberti and Li-Qiang Chu },
url = {https://www.sciencedirect.com/science/article/pii/S0378517321006098},
doi = {10.1016/j.ijpharm.2021.120804},
isbn = {218995},
year = {2021},
date = {2021-06-16},
journal = {International Journal of Pharmaceutics},
volume = {605},
number = {120804},
abstract = {Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72×10-6 cm2/s to 4.50×10-6 cm2/s. The gelation kinetics then is described with a “zero order” mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72×10-6 cm2/s to 4.50×10-6 cm2/s. The gelation kinetics then is described with a “zero order” mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel.2019
Caccavo, Diego
An overview on the mathematical modeling of hydrogels’ behavior for drug delivery systems Journal Article
In: International Journal of Pharmaceutics, vol. 560, pp. 175-190, 2019.
@article{Caccavo2019,
title = {An overview on the mathematical modeling of hydrogels’ behavior for drug delivery systems},
author = {Diego Caccavo},
url = {https://www.sciencedirect.com/science/article/pii/S0378517319301188?via%3Dihub},
doi = {10.1016/j.ijpharm.2019.01.076},
year = {2019},
date = {2019-02-11},
journal = {International Journal of Pharmaceutics},
volume = {560},
pages = {175-190},
abstract = {Hydrogels-based systems (HBSs) for drug delivery are nowadays extensively used and the interest in modeling their behavior is dramatically increasing. In this review a critical overview on the modeling approaches is given, quantitatively and qualitatively analyzing the publications on the subject, the trend of the publications per year and the type of modeling approaches. It was found that, despite the drug release fitting models (i.e. Higuchi’s equation) are the most abundant, their use for HBSs is decreasing in the last years and luckily, considering the limiting assumption on which they were built, they will be confined to simple mathematical fitting equations. Within the mechanistic models the “multi-component” with the swelling approximation (mass transport only) and with the mechanics (fully coupled) are experiencing the highest growth rate, with much more interest toward the last one that, in the next years could be able to provide a first principles model. Statistical models, especially based on the response surface methodology, are rapidly spreading in the scientific community mainly thanks to their ability to be predictive, regardless of the phenomenology, in the analyzed design space with very low efforts. Neural Networks models for HBSs, in countertrend with their use in the pharmaceutical industry, have never take off preferring less data demanding statistical models.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels-based systems (HBSs) for drug delivery are nowadays extensively used and the interest in modeling their behavior is dramatically increasing. In this review a critical overview on the modeling approaches is given, quantitatively and qualitatively analyzing the publications on the subject, the trend of the publications per year and the type of modeling approaches. It was found that, despite the drug release fitting models (i.e. Higuchi’s equation) are the most abundant, their use for HBSs is decreasing in the last years and luckily, considering the limiting assumption on which they were built, they will be confined to simple mathematical fitting equations. Within the mechanistic models the “multi-component” with the swelling approximation (mass transport only) and with the mechanics (fully coupled) are experiencing the highest growth rate, with much more interest toward the last one that, in the next years could be able to provide a first principles model. Statistical models, especially based on the response surface methodology, are rapidly spreading in the scientific community mainly thanks to their ability to be predictive, regardless of the phenomenology, in the analyzed design space with very low efforts. Neural Networks models for HBSs, in countertrend with their use in the pharmaceutical industry, have never take off preferring less data demanding statistical models.2018
Caccavo, Diego; Vietri, Antonella; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Modeling the mechanics and the transport phenomena in hydrogels Book Chapter
In: Manca, Davide (Ed.): Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications, Chapter 12, 2018.
@inbook{Caccavo2018b,
title = {Modeling the mechanics and the transport phenomena in hydrogels},
author = {Diego Caccavo and Antonella Vietri and Gaetano Lamberti and Anna Angela Barba and Anette Larsson },
editor = {Davide Manca},
url = {https://www.sciencedirect.com/science/article/pii/B978044463964600012X},
doi = {10.1016/B978-0-444-63964-6.00012-X},
year = {2018},
date = {2018-07-18},
booktitle = {Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications},
chapter = {12},
abstract = {Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as\textemdashin principle\textemdashany other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as—in principle—any other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour Journal Article
In: Chemical Society Reviews, vol. 47, no. 7, pp. 2357-2373, 2018, ISSN: 0306-0012.
@article{Caccavo2018,
title = {Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://pubs.rsc.org/en/content/articlelanding/2018/cs/c7cs00638a#!divAbstract},
doi = {10.1039/C7CS00638A},
issn = {0306-0012},
year = {2018},
date = {2018-04-07},
journal = {Chemical Society Reviews},
volume = {47},
number = {7},
pages = {2357-2373},
abstract = {Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure\textendashproperty relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure–property relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.2017
Caccavo, Diego; Barba, Anna Angela; D'Amore, Matteo; Piano, Raffaella De; Lamberti, Gaetano; Rossi, Alessandra; Colombo, Paolo
Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix® Journal Article
In: European Journal of Pharmaceutics and Biopharmaceutics, vol. 121, pp. 24-31, 2017, ISSN: 0939-6411.
@article{Caccavo2017b,
title = {Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®},
author = {Diego Caccavo and Anna Angela Barba and Matteo D'Amore and Raffaella {De Piano} and Gaetano Lamberti and Alessandra Rossi and Paolo Colombo},
url = {http://www.sciencedirect.com/science/article/pii/S0939641117308366},
doi = {10.1016/j.ejpb.2017.08.016},
issn = {0939-6411},
year = {2017},
date = {2017-12-01},
journal = {European Journal of Pharmaceutics and Biopharmaceutics},
volume = {121},
pages = {24-31},
abstract = {The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Abrahmsén-Alami, Susanna; Viridén, Anna; Larsson, Anette
Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study Journal Article
In: International Journal of Pharmaceutics, vol. 528, no. 1-2, pp. 705-713, 2017, ISSN: 0378-5173.
@article{Larsson2017,
title = {Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study},
author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Susanna Abrahms\'{e}n-Alami and Anna Virid\'{e}n and Anette Larsson},
url = {http://www.sciencedirect.com/science/article/pii/S0378517317305720},
doi = {10.1016/j.ijpharm.2017.06.064},
issn = {0378-5173},
year = {2017},
date = {2017-08-07},
journal = {International Journal of Pharmaceutics},
volume = {528},
number = {1-2},
pages = {705-713},
abstract = {The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices.Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela
Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications Journal Article
In: Natural Product Communications, vol. 12, no. 6, pp. 867-871, 2017, ISSN: 1934-578X.
@article{NPC02,
title = {Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Annalisa Dalmoro and Anna Angela Barba},
url = {http://www.naturalproduct.us/index.asp
https://www.gruppotpp.it/wp-content/uploads/2017/06/Caccavo-et-al-NPC-126-867-871-2017-Abstract.pdf},
issn = {1934-578X},
year = {2017},
date = {2017-07-31},
journal = {Natural Product Communications},
volume = {12},
number = {6},
pages = {867-871},
abstract = {Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources.
In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources.
In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications.
Caccavo, Diego; Lamberti, Gaetano
PoroViscoElastic model to describe hydrogels' behavior Journal Article
In: Materials Science and Engineering: C, vol. 76, pp. 102–113, 2017.
@article{Caccavo2017,
title = {PoroViscoElastic model to describe hydrogels' behavior},
author = {Diego Caccavo and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0928493116325760},
doi = {10.1016/j.msec.2017.02.155},
year = {2017},
date = {2017-07-01},
journal = {Materials Science and Engineering: C},
volume = {76},
pages = {102\textendash113},
abstract = {Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior.Caccavo, Diego; Cascone, Sara; Poto, Serena; Lamberti, Gaetano; Barba, Anna Angela
Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests Journal Article
In: Carbohydrate Polymers, vol. 167, pp. 136–144, 2017.
@article{Caccavo2017b,
title = {Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests},
author = {Diego Caccavo and Sara Cascone and Serena Poto and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0144861717302837},
doi = {10.1016/j.carbpol.2017.03.027},
year = {2017},
date = {2017-07-01},
journal = {Carbohydrate Polymers},
volume = {167},
pages = {136\textendash144},
abstract = {Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior.Caccavo, Diego; Lamberti, Gaetano; Cafaro, Maria Margherita; Barba, Anna Angela; Kazlauske, Jurgita; Larsson, Anette
Mathematical modeling of the drug release from an ensemble of coated pellets Journal Article
In: British Journal of Pharmacology, vol. 174, no. 12, pp. 1797–1809 , 2017, ISBN: 1476-5381.
@article{Caccavo2017b,
title = {Mathematical modeling of the drug release from an ensemble of coated pellets},
author = {Diego Caccavo and Gaetano Lamberti and Maria Margherita Cafaro and Anna Angela Barba and Jurgita Kazlauske and Anette Larsson},
url = {http://onlinelibrary.wiley.com/doi/10.1111/bph.13776/abstract},
doi = {10.1111/bph.13776},
isbn = {1476-5381},
year = {2017},
date = {2017-04-22},
journal = {British Journal of Pharmacology},
volume = {174},
number = {12},
pages = {1797\textendash1809 },
abstract = {Background and Purpose
Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models.
Experimental approach
In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets.
Key Results
In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release.
Conclusions and Implications
The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background and Purpose
Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models.
Experimental approach
In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets.
Key Results
In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release.
Conclusions and Implications
The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Drug delivery from hydrogels: a general framework for the release modeling Journal Article
In: Current Drug Delivery, vol. 14, no. 2, pp. 179 - 189, 2017.
@article{Caccavo2016b,
title = {Drug delivery from hydrogels: a general framework for the release modeling},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson },
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/03.-Caccavo-et-al-CDD-142-179-189-2017.pdf
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/179/},
doi = {10.2174/1567201813666160808102106},
year = {2017},
date = {2017-02-08},
issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},
journal = {Current Drug Delivery},
volume = {14},
number = {2},
pages = {179 - 189},
abstract = {The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.},
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The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.2016
Lamberti, Gaetano; Barba, Anna Angela; Cascone, Sara; Dalmoro, Annalisa; Caccavo, Diego
An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications Book Chapter
In: Majee, Sutapa Biswas (Ed.): Emerging Concepts in Analysis and Applications of Hydrogels, Chapter 8, Intech, 2016, ISBN: 978-953-51-2510-5.
@inbook{Lamberti2016b,
title = {An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications},
author = {Gaetano Lamberti and Anna Angela Barba and Sara Cascone and Annalisa Dalmoro and Diego Caccavo},
editor = {Sutapa Biswas Majee},
url = {http://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-of-hydrogels/an-engineering-point-of-view-on-the-use-of-the-hydrogels-for-pharmaceutical-and-biomedical-applicati},
doi = {10.5772/64299 },
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year = {2016},
date = {2016-08-24},
booktitle = {Emerging Concepts in Analysis and Applications of Hydrogels},
publisher = {Intech},
chapter = {8},
abstract = {In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.},
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In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Swellable Hydrogel-based Systems for Controlled Drug Delivery Book Chapter
In: Sezer, Ali Demir (Ed.): Smart Drug Delivery System, Chapter 10, Intech, 2016, ISBN: 978-953-51-2247-0.
@inbook{Caccavo2016b,
title = {Swellable Hydrogel-based Systems for Controlled Drug Delivery},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson},
editor = {Ali Demir Sezer},
url = {http://www.intechopen.com/books/smart-drug-delivery-system/swellable-hydrogel-based-systems-for-controlled-drug-delivery#exportas},
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abstract = {The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass\textendashrubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.},
keywords = {},
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}
The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass–rubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.Caccavo, Diego; Ström, Anna; Larsson, Anette; Lamberti, Gaetano
Modeling capillary formation in calcium and copper alginate gels Journal Article
In: Materials Science and Engineering: C, vol. 58, pp. 442–449, 2016, ISSN: 09284931.
@article{Caccavo2016,
title = {Modeling capillary formation in calcium and copper alginate gels},
author = { Diego Caccavo and Anna Str\"{o}m and Anette Larsson and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0928493115302940},
doi = {10.1016/j.msec.2015.08.040},
issn = {09284931},
year = {2016},
date = {2016-01-01},
journal = {Materials Science and Engineering: C},
volume = {58},
pages = {442--449},
abstract = {Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.},
keywords = {},
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Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.2015
Caccavo, Diego; Lamberti, Gaetano; Cascone, Sara; Barba, Anna Angela; Larsson, Anette
Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment Journal Article
In: Carbohydrate Polymers, vol. 131, pp. 41–49, 2015, ISSN: 01448617.
@article{Caccavo2015b,
title = {Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment},
author = { Diego Caccavo and Gaetano Lamberti and Sara Cascone and Anna Angela Barba and Anette Larsson},
url = {http://www.sciencedirect.com/science/article/pii/S0144861715004476},
doi = {10.1016/j.carbpol.2015.05.041},
issn = {01448617},
year = {2015},
date = {2015-10-01},
journal = {Carbohydrate Polymers},
volume = {131},
pages = {41--49},
abstract = {The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.Abrahmsén-Alami, Susanna; Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Viridén, Anna; Larsson, Anette
Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach Journal Article
In: AstraZeneca Internal Journal, pp. 1-2, 2015.
@article{Abrahms\'{e}n-Alami2015,
title = {Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach},
author = {Susanna Abrahms\'{e}n-Alami and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Anna Virid\'{e}n and Anette Larsson},
year = {2015},
date = {2015-09-01},
journal = {AstraZeneca Internal Journal},
pages = {1-2},
abstract = {In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior \textendash as well as for the design \textendash of the tablets based on hydrogels.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior – as well as for the design – of the tablets based on hydrogels.Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Hydrogel-Based CRSs Analyses: Testing And Modeling Proceedings Article
In: 1st International Congress of Controlled Release Society - Greek Local Chapter, pp. 1–1, 1st International Congress of Controlled Release Society, Athens (Greece), 2015.
@inproceedings{caccavo2015b,
title = {Hydrogel-Based CRSs Analyses: Testing And Modeling},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
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booktitle = {1st International Congress of Controlled Release Society - Greek Local Chapter},
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Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Controlled drug release from hydrogel-based matrices: Experiments and modeling. Journal Article
In: International journal of pharmaceutics, vol. 486, no. 1-2, pp. 144–152, 2015, ISSN: 1873-3476.
@article{Caccavo2015a,
title = {Controlled drug release from hydrogel-based matrices: Experiments and modeling.},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0378517315002707},
doi = {10.1016/j.ijpharm.2015.03.054},
issn = {1873-3476},
year = {2015},
date = {2015-03-01},
journal = {International journal of pharmaceutics},
volume = {486},
number = {1-2},
pages = {144--152},
abstract = {Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Modeling the Drug Release from Hydrogel-Based Matrices Journal Article
In: Molecular Pharmaceutics, vol. 12, no. 2, pp. 474–483, 2015, ISSN: 1543-8384.
@article{Caccavo2015c,
title = {Modeling the Drug Release from Hydrogel-Based Matrices},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://pubs.acs.org/doi/abs/10.1021/mp500563n},
doi = {10.1021/mp500563n},
issn = {1543-8384},
year = {2015},
date = {2015-02-01},
journal = {Molecular Pharmaceutics},
volume = {12},
number = {2},
pages = {474--483},
publisher = {American Chemical Society},
chapter = {474},
keywords = {},
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2014
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications Proceedings Article
In: Proceedings of CHISA 2014, pp. 1–1, CHISA 2014, Prague, Czech Republic, 2014.
@inproceedings{d.2014,
title = {Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
year = {2014},
date = {2014-08-01},
booktitle = {Proceedings of CHISA 2014},
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address = {Prague, Czech Republic},
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Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela
MODELING THE BEHAVIOR OF SWELLABLE HYDROGELS-BASED MATRICES FOR PHARMACEUTICAL APPLICATIONS Proceedings Article
In: 13th European Symposium on Controlled Drug Delivery, pp. 3–4, ESCDD 2014, Egmond aan Zee, The Netherlands, 2014.
@inproceedings{s.2014,
title = {MODELING THE BEHAVIOR OF SWELLABLE HYDROGELS-BASED MATRICES FOR PHARMACEUTICAL APPLICATIONS},
author = { Sara Cascone and Diego Caccavo and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},
year = {2014},
date = {2014-04-01},
booktitle = {13th European Symposium on Controlled Drug Delivery},
pages = {3--4},
publisher = {ESCDD 2014},
address = {Egmond aan Zee, The Netherlands},
keywords = {},
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Barba, Anna Angela; Lamberti, Gaetano; Rabbia, Luca; Grassi, Mario; Larobina, Domenico; Grassi, Gabriele
Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications Journal Article
In: Materials Science and Engineering: C, vol. 37, pp. 327–331, 2014, ISSN: 09284931.
@article{Barba2014b,
title = {Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications},
author = { Anna Angela Barba and Gaetano Lamberti and Luca Rabbia and Mario Grassi and Domenico Larobina and Gabriele Grassi},
url = {http://www.sciencedirect.com/science/article/pii/S0928493114000423},
doi = {10.1016/j.msec.2014.01.034},
issn = {09284931},
year = {2014},
date = {2014-01-01},
journal = {Materials Science and Engineering: C},
volume = {37},
pages = {327--331},
abstract = {In this work, blends of alginate/pluronic (F127) for biomedical applications were investigated. In particular, the kinetics of alginate chain reticulation by bivalent cations was studied by experimental and modeling approaches. Two kinds of sodium alginate were tested to obtain hard gel films. The thicknesses of the reticulated alginate films were measured as function of the exposure time and of the reticulating copper (Cu2+) solution concentration. The kinetics was described by a proper model able to reproduce the experimental data. The model parameters, evaluated based on the measurements of thicknesses as function of Cu2+ concentration and exposure time, were further validated by comparing the prediction of the model with another set of independent measurement; here, the depletion of Cu2+ ions in the conditioning solution above the reacting gel is measured as function of time. The tuned model could be used in the description of the future applications of the blends.},
keywords = {},
pubstate = {published},
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}
In this work, blends of alginate/pluronic (F127) for biomedical applications were investigated. In particular, the kinetics of alginate chain reticulation by bivalent cations was studied by experimental and modeling approaches. Two kinds of sodium alginate were tested to obtain hard gel films. The thicknesses of the reticulated alginate films were measured as function of the exposure time and of the reticulating copper (Cu2+) solution concentration. The kinetics was described by a proper model able to reproduce the experimental data. The model parameters, evaluated based on the measurements of thicknesses as function of Cu2+ concentration and exposure time, were further validated by comparing the prediction of the model with another set of independent measurement; here, the depletion of Cu2+ ions in the conditioning solution above the reacting gel is measured as function of time. The tuned model could be used in the description of the future applications of the blends.2012
Barba, Anna Angela; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo
MODELING OF CONTROLLED DRUG RELEASE FROM HYDROGEL-BASED MATRICES Proceedings Article
In: Biomaterials: from drug delivery to tissue engineering, pp. 1–2, Palermo, 2012.
@inproceedings{a.a.2012,
title = {MODELING OF CONTROLLED DRUG RELEASE FROM HYDROGEL-BASED MATRICES},
author = { Anna Angela Barba and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore},
year = {2012},
date = {2012-11-01},
booktitle = {Biomaterials: from drug delivery to tissue engineering},
pages = {1--2},
address = {Palermo},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Galdi, Ivan; Lamberti, Gaetano
Drug release from matrix systems: analysis by finite element methods Journal Article
In: Heat and Mass Transfer, vol. 48, no. 3, pp. 519–528, 2012, ISSN: 0947-7411.
@article{Galdi2012,
title = {Drug release from matrix systems: analysis by finite element methods},
author = { Ivan Galdi and Gaetano Lamberti},
url = {http://link.springer.com/10.1007/s00231-011-0900-y},
doi = {10.1007/s00231-011-0900-y},
issn = {0947-7411},
year = {2012},
date = {2012-03-01},
journal = {Heat and Mass Transfer},
volume = {48},
number = {3},
pages = {519--528},
abstract = {In this work some problems in drug delivery from solid systems were described in terms of transient mass balances with diffusion and solved by using FEM. Firstly, the solving codes were compared with known analytical solutions, available for simple problems (simple geometries, constant diffusivities). Then, models were written to describe more realistic systems (complex geometries, variable diffusivities). Eventually, the behaviors of some real drug delivery systems were successfully predicted.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work some problems in drug delivery from solid systems were described in terms of transient mass balances with diffusion and solved by using FEM. Firstly, the solving codes were compared with known analytical solutions, available for simple problems (simple geometries, constant diffusivities). Then, models were written to describe more realistic systems (complex geometries, variable diffusivities). Eventually, the behaviors of some real drug delivery systems were successfully predicted.Lamberti, Gaetano; Cascone, Sara; Titomanlio, Giuseppe; Barba, Anna Angela
Controlled Release of Drugs From Hydrogel Based Matrices Systems: Experiments and Modeling Journal Article
In: Chemical and Biochemical Engineering Quarterly, vol. 26, no. 4, pp. 321–330, 2012, ISSN: 0352-9568.
@article{Lamberti2012c,
title = {Controlled Release of Drugs From Hydrogel Based Matrices Systems: Experiments and Modeling},
author = { Gaetano Lamberti and Sara Cascone and Giuseppe Titomanlio and Anna Angela Barba},
issn = {0352-9568},
year = {2012},
date = {2012-01-01},
journal = {Chemical and Biochemical Engineering Quarterly},
volume = {26},
number = {4},
pages = {321--330},
publisher = {Hrvatsko dru\v{s}tvo kemijskih in\v{z}enjera i tehnologa},
abstract = {Hydrogels are materials largely used in the formulation of pharmaceuticals since, in principle, they could produce a release system of zero-order kinetics, which is of great therapeutic interest. In this paper, a model was proposed for the description of the main transport phenomena involved in the drug release process from hydrogel matrices (water diffusion, polymer swelling, drug diffusion and polymer dissolution); the model predictions are successfully compared with a large set of experimental data, obtained working with matrices systems based on HPMC (Hydroxy Propyl Methyl Cellulose). The proposed model was found able to reproduce main features of the observed phenomena, it can thus be adopted for prediction of the performances of drug release systems from hydrogel matrices.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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Hydrogels are materials largely used in the formulation of pharmaceuticals since, in principle, they could produce a release system of zero-order kinetics, which is of great therapeutic interest. In this paper, a model was proposed for the description of the main transport phenomena involved in the drug release process from hydrogel matrices (water diffusion, polymer swelling, drug diffusion and polymer dissolution); the model predictions are successfully compared with a large set of experimental data, obtained working with matrices systems based on HPMC (Hydroxy Propyl Methyl Cellulose). The proposed model was found able to reproduce main features of the observed phenomena, it can thus be adopted for prediction of the performances of drug release systems from hydrogel matrices.2011
Lamberti, Gaetano; Galdi, Ivan; Barba, Anna Angela
Controlled release from hydrogel-based solid matrices. A model accounting for water up-take, swelling and erosion. Journal Article
In: International journal of pharmaceutics, vol. 407, no. 1-2, pp. 78–86, 2011, ISSN: 1873-3476.
@article{Lamberti2011,
title = {Controlled release from hydrogel-based solid matrices. A model accounting for water up-take, swelling and erosion.},
author = { Gaetano Lamberti and Ivan Galdi and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0378517311000548},
doi = {10.1016/j.ijpharm.2011.01.023},
issn = {1873-3476},
year = {2011},
date = {2011-04-01},
journal = {International journal of pharmaceutics},
volume = {407},
number = {1-2},
pages = {78--86},
abstract = {Design and realization of drug delivery systems based on polymer matrices could be greatly improved by modeling the phenomena which take place after the systems administration. Availability of a reliable mathematical model, able to predict the release kinetic from drug delivery systems, could actually replace the resource-consuming trial-and-error procedures usually followed in the manufacture of these latter. In this work, the complex problem of drug release from polymer (HPMC) based matrices systems was faced. The phenomena, previously observed and experimentally quantified, of water up-take, system swelling and erosion, and drug release were here described by transient mass balances with diffusion. The resulting set of differential equations was solved by using finite element methods. Two different systems were investigated: cylindrical matrices in which the transport phenomena were allowed only by lateral surfaces ("radial" case), and cylindrical matrices with the overall surface exposed to the solvent ("overall" case). A code able to describe quantitatively all the observed phenomena has been obtained.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Design and realization of drug delivery systems based on polymer matrices could be greatly improved by modeling the phenomena which take place after the systems administration. Availability of a reliable mathematical model, able to predict the release kinetic from drug delivery systems, could actually replace the resource-consuming trial-and-error procedures usually followed in the manufacture of these latter. In this work, the complex problem of drug release from polymer (HPMC) based matrices systems was faced. The phenomena, previously observed and experimentally quantified, of water up-take, system swelling and erosion, and drug release were here described by transient mass balances with diffusion. The resulting set of differential equations was solved by using finite element methods. Two different systems were investigated: cylindrical matrices in which the transport phenomena were allowed only by lateral surfaces ("radial" case), and cylindrical matrices with the overall surface exposed to the solvent ("overall" case). A code able to describe quantitatively all the observed phenomena has been obtained.2010
Galdi, Ivan; Dalmoro, Annalisa; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela; D'Amore, Matteo
Modeling of the controlled drug release from solid matrices based on swellable/erodible polymeric hydrogels Proceedings Article
In: Proceedings of CHISA 2010 - ECCE 7, pp. 1–3, Chisa 2010, Praha, Czech Republic, 2010.
@inproceedings{i.2010,
title = {Modeling of the controlled drug release from solid matrices based on swellable/erodible polymeric hydrogels},
author = { Ivan Galdi and Annalisa Dalmoro and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba and Matteo D'Amore},
year = {2010},
date = {2010-08-01},
booktitle = {Proceedings of CHISA 2010 - ECCE 7},
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Galdi, Ivan; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela; D'Amore, Matteo
Modeling drug release from solid matrices based on polymeric hydrogels Proceedings Article
In: PPS 26, pp. 1–6, Polymer Processing Society, Banff (Canada), 2010.
@inproceedings{galdi2010,
title = {Modeling drug release from solid matrices based on polymeric hydrogels},
author = { Ivan Galdi and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba and Matteo D'Amore},
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Galdi, Ivan; Dalmoro, Annalisa; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela; D'Amore, Matteo
Swelling, erosion and drug release in hydrogel based solid matrices Proceedings Article
In: Proceedings on CD-ROM of PBP 7, pp. 1–4, PBP, La Valletta, Malta, 2010.
@inproceedings{galdi2010-2,
title = {Swelling, erosion and drug release in hydrogel based solid matrices},
author = { Ivan Galdi and Annalisa Dalmoro and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba and Matteo D'Amore},
year = {2010},
date = {2010-03-01},
booktitle = {Proceedings on CD-ROM of PBP 7},
pages = {1--4},
publisher = {PBP},
address = {La Valletta, Malta},
keywords = {},
pubstate = {published},
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2009
Barba, Anna Angela; D'Amore, Matteo; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe
A general code to predict the drug release kinetics from different shaped matrices. Journal Article
In: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, vol. 36, no. 2-3, pp. 359–68, 2009, ISSN: 1879-0720.
@article{Barba2009c,
title = {A general code to predict the drug release kinetics from different shaped matrices.},
author = { Anna Angela Barba and Matteo D'Amore and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S0928098708004338},
doi = {10.1016/j.ejps.2008.10.006},
issn = {1879-0720},
year = {2009},
date = {2009-01-01},
journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences},
volume = {36},
number = {2-3},
pages = {359--68},
abstract = {This work deals with the modeling of drug release from solid pharmaceutical systems (matrices) for oral delivery. The attention was paid to the behavior of matrices made of hydrogels and drug, and the modeling was devoted to reproduce all the relevant phenomena (water up-take, gel swelling, diffusivity increase, drug diffusion and polymer erosion). Thus, the transient mass balances (for both drug and water), with the proper initial and boundary conditions were written, and a generalized numerical code was formulated; it is able to describe several geometries (slab, sphere, infinite and finite cylinders; this latter was done by an approximation which reduces the 2D problem to an 1D scheme). The main phenomena observed in drug delivery from hydrogel-based matrix, i.e. polymer swelling and erosion, were taken into account. The code was validated by comparison with analytical solutions, available for some simplified situation, and then it was tested with some experimental data taken from literature.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This work deals with the modeling of drug release from solid pharmaceutical systems (matrices) for oral delivery. The attention was paid to the behavior of matrices made of hydrogels and drug, and the modeling was devoted to reproduce all the relevant phenomena (water up-take, gel swelling, diffusivity increase, drug diffusion and polymer erosion). Thus, the transient mass balances (for both drug and water), with the proper initial and boundary conditions were written, and a generalized numerical code was formulated; it is able to describe several geometries (slab, sphere, infinite and finite cylinders; this latter was done by an approximation which reduces the 2D problem to an 1D scheme). The main phenomena observed in drug delivery from hydrogel-based matrix, i.e. polymer swelling and erosion, were taken into account. The code was validated by comparison with analytical solutions, available for some simplified situation, and then it was tested with some experimental data taken from literature.Barba, Anna Angela; Lamberti, Gaetano
Verso un rilascio intelligente Journal Article
In: NCF-Notiziario Chimico Farmaceutico, vol. 48, no. 1, pp. 68–71, 2009, ISSN: 0393-3733.
@article{Barba2009b,
title = {Verso un rilascio intelligente},
author = { Anna Angela Barba and Gaetano Lamberti},
issn = {0393-3733},
year = {2009},
date = {2009-01-01},
journal = {NCF-Notiziario Chimico Farmaceutico},
volume = {48},
number = {1},
pages = {68--71},
abstract = {L’efficacia di una terapia farmacologica dipende molto dal profi lo di rilascio del principio attivo dalla forma farmaceutica selezionata. In riferimento alla via di somministrazione orale, comprendere i fenomeni che si verificano dopo l’ingestione di una compressa \'{e} un passaggio fondamentale per poter ottimizzare le formulazioni e le tecniche di preparazione. Investigare tali fenomeni \'{e} uno degli scopi della nostra ricerca, e nell’articolo sono presentati e discussi alcuni risultati selezionati.},
keywords = {},
pubstate = {published},
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L’efficacia di una terapia farmacologica dipende molto dal profi lo di rilascio del principio attivo dalla forma farmaceutica selezionata. In riferimento alla via di somministrazione orale, comprendere i fenomeni che si verificano dopo l’ingestione di una compressa é un passaggio fondamentale per poter ottimizzare le formulazioni e le tecniche di preparazione. Investigare tali fenomeni é uno degli scopi della nostra ricerca, e nell’articolo sono presentati e discussi alcuni risultati selezionati.2007
Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
Analysis and modeling of Diclofenac Sodium release kinetics from HPMC tablets Proceedings Article
In: Proceedings of European Congress of Chemical Engineering (ECCE-6), pp. 253–254, Copenhagen, 2007.
@inproceedings{barba2007,
title = {Analysis and modeling of Diclofenac Sodium release kinetics from HPMC tablets},
author = { Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
year = {2007},
date = {2007-09-01},
booktitle = {Proceedings of European Congress of Chemical Engineering (ECCE-6)},
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address = {Copenhagen},
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Chirico, Serafina; Lamberti, Gaetano; NUNZIATA, V; Titomanlio, Giuseppe
Analysis and modeling of radial water up-take in pure HPMC tablets Proceedings Article
In: Proceedings of European Congress of Chemical Engineering (ECCE-6), pp. 251–252, Copenhagen, 2007.
@inproceedings{chirico2007b,
title = {Analysis and modeling of radial water up-take in pure HPMC tablets},
author = { Serafina Chirico and Gaetano Lamberti and V NUNZIATA and Giuseppe Titomanlio},
year = {2007},
date = {2007-09-01},
booktitle = {Proceedings of European Congress of Chemical Engineering (ECCE-6)},
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Chirico, Serafina; Dalmoro, Annalisa; Lamberti, Gaetano; Russo, Giuseppina; Titomanlio, Giuseppe
Analysis and modeling of swelling and erosion behavior for pure HPMC tablet Journal Article
In: Journal of Controlled Release, vol. 122, no. 2, pp. 181–188, 2007, ISSN: 01683659.
@article{Chirico2007,
title = {Analysis and modeling of swelling and erosion behavior for pure HPMC tablet},
author = { Serafina Chirico and Annalisa Dalmoro and Gaetano Lamberti and Giuseppina Russo and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S0168365907003215},
doi = {10.1016/j.jconrel.2007.07.001},
issn = {01683659},
year = {2007},
date = {2007-09-01},
journal = {Journal of Controlled Release},
volume = {122},
number = {2},
pages = {181--188},
abstract = {This work is focused on the transport phenomena which take place during immersion in water of pure hydroxypropylmethylcellulose tablets. The water uptake, the swelling and the erosion during immersion were investigated in drug-free systems, as a preliminary task before to undertake the study of drug-loaded ones. The tablets, obtained by powder compression, were confined between glass slabs to allow water uptake only by lateral surface and then immersed in distilled water at 37 °C, with simultaneous video-recording. By image analysis the normalized light intensity profiles were obtained and taken as a measure of the water mass fraction. The time evolutions of the total tablet mass, of the water mass and of the erosion radius were measured, too. Thus a novel method to measure polymer and water masses during hydration was pointed out. Then, a model consisting in the transient mass balance, accounting for water diffusion, diffusivity change due to hydration, swelling and erosion, was found able to reproduce all experimental data. Even if the model was already used in literature, the novelty of our approach is to compare model predictions with a complete set of experimental data, confirming that the main phenomena were correctly identified and described.},
keywords = {},
pubstate = {published},
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}
This work is focused on the transport phenomena which take place during immersion in water of pure hydroxypropylmethylcellulose tablets. The water uptake, the swelling and the erosion during immersion were investigated in drug-free systems, as a preliminary task before to undertake the study of drug-loaded ones. The tablets, obtained by powder compression, were confined between glass slabs to allow water uptake only by lateral surface and then immersed in distilled water at 37 °C, with simultaneous video-recording. By image analysis the normalized light intensity profiles were obtained and taken as a measure of the water mass fraction. The time evolutions of the total tablet mass, of the water mass and of the erosion radius were measured, too. Thus a novel method to measure polymer and water masses during hydration was pointed out. Then, a model consisting in the transient mass balance, accounting for water diffusion, diffusivity change due to hydration, swelling and erosion, was found able to reproduce all experimental data. Even if the model was already used in literature, the novelty of our approach is to compare model predictions with a complete set of experimental data, confirming that the main phenomena were correctly identified and described.Cascone, Sara; Chirico, Serafina; Lamberti, Gaetano; Titomanlio, Giuseppe
Water and theopylline transport phenomena within HPMC based tablets Proceedings Article
In: Proceedings of Innovation in Drug Delivery, pp. 1–2, Napoli, 2007.
@inproceedings{cascone2007-1,
title = {Water and theopylline transport phenomena within HPMC based tablets},
author = { Sara Cascone and Serafina Chirico and Gaetano Lamberti and Giuseppe Titomanlio},
year = {2007},
date = {2007-09-01},
booktitle = {Proceedings of Innovation in Drug Delivery},
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address = {Napoli},
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2006
Chirico, Serafina; Lamberti, Gaetano; Russo, Giuseppina; Titomanlio, Giuseppe
Swelling and erosion kinetics of HPMC based system for controlled drug release Proceedings Article
In: pp. x, Ischia (NA), 2006.
@inproceedings{chirico2006-1,
title = {Swelling and erosion kinetics of HPMC based system for controlled drug release},
author = { Serafina Chirico and Gaetano Lamberti and Giuseppina Russo and Giuseppe Titomanlio},
year = {2006},
date = {2006-01-01},
pages = {x},
address = {Ischia (NA)},
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pubstate = {published},
tppubtype = {inproceedings}
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0000
Barba, Anna Angela; Chirico, Serafina; D'Amore, Matteo; Lamberti, Gaetano; Titomanlio, Giuseppe
Hydration, swelling , erosion and drug release from HPMC and HPMC/TP Proceedings Article
In: pp. 61–64, Piano di Sorrento (NA), Italia, 0000.
@inproceedings{barba2008-4,
title = {Hydration, swelling , erosion and drug release from HPMC and HPMC/TP},
author = { Anna Angela Barba and Serafina Chirico and Matteo D'Amore and Gaetano Lamberti and Giuseppe Titomanlio},
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Chirico, Serafina; Dalmoro, Annalisa; Lamberti, Gaetano; Russo, Giuseppina; Titomanlio, Giuseppe
Radial water up-take in pure HPMC tablet: analysis and model prediction Proceedings Article
In: Proceedings of Pharmaceutical Science World Congress, pp. 1–4, Amsterdam, 0000.
@inproceedings{chirico2007-1,
title = {Radial water up-take in pure HPMC tablet: analysis and model prediction},
author = { Serafina Chirico and Annalisa Dalmoro and Gaetano Lamberti and Giuseppina Russo and Giuseppe Titomanlio},
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Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
Analysis of Mass Transfer during Controlled Release of Diclofenac from Commercial Tablets Proceedings Article
In: pp. x, Vienna (Austria), 0000.
@inproceedings{barba2006,
title = {Analysis of Mass Transfer during Controlled Release of Diclofenac from Commercial Tablets},
author = { Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
pages = {x},
address = {Vienna (Austria)},
keywords = {},
pubstate = {published},
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}
Lamberti, Gaetano; Barba, Anna Angela; Coviello, Antonio; Titomanlio, Giuseppe
Modeling Transport Phenomena during Controlled Release from Various Shaped Tablets Proceedings Article
In: pp. x, Vienna, 0000.
@inproceedings{lamberti2006-1,
title = {Modeling Transport Phenomena during Controlled Release from Various Shaped Tablets},
author = { Gaetano Lamberti and Anna Angela Barba and Antonio Coviello and Giuseppe Titomanlio},
pages = {x},
address = {Vienna},
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