@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 = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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.},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Alginate, Gel capillaries, Hydrogel Characterization, Hydrogel Modeling, Ionotropic gelation, Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Modeling, Texture analysis, Transport phenomena, Water uptake},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Alginate, Hydrogel Modeling, Modeling, Pluronic, Reticulation},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {drug release, Hydrogel Modeling, Hydrogels, Mathematical modeling, Swelling; Erosion},

pubstate = {published},

tppubtype = {article}

}

@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 = {drug release, Hydrogel Modeling, Matrix geometry, Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Controlled drug release, Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Swelling},

pubstate = {published},

tppubtype = {article}

}