The publications of the members of the research group.
2019
Simone, Veronica De; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela
Effect of binder and load solubility properties on HPMC granules produced by wet granulation process Journal Article
In: Journal of Drug Delivery Science and Technology, vol. 49, pp. 513-520, 2019.
Abstract | Links | BibTeX | Tags: Granulation, HPMC
@article{Simone}2019,
title = {Effect of binder and load solubility properties on HPMC granules produced by wet granulation process},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/pii/S1773224718311043},
doi = {10.1016/j.jddst.2018.12.030},
year = {2019},
date = {2019-02-01},
journal = {Journal of Drug Delivery Science and Technology},
volume = {49},
pages = {513-520},
abstract = {Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.},
keywords = {Granulation, HPMC},
pubstate = {published},
tppubtype = {article}
}
Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.
2018
Simone, Veronica De; Caccavo, Diego; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Wet-granulation process: phenomenological analysis and process parameters optimization Journal Article
In: Powder Technology, vol. 340, pp. 411-419, 2018.
Abstract | Links | BibTeX | Tags: Granulation, HPMC
@article{Simone}2018b,
title = {Wet-granulation process: phenomenological analysis and process parameters optimization},
author = {Veronica {De Simone} and Diego Caccavo and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/pii/S0032591018307800},
doi = {10.1016/j.powtec.2018.09.053},
year = {2018},
date = {2018-12-01},
journal = {Powder Technology},
volume = {340},
pages = {411-419},
abstract = {Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000\textendash10,000 μm) as the main variable of interest.},
keywords = {Granulation, HPMC},
pubstate = {published},
tppubtype = {article}
}
Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000–10,000 μm) as the main variable of interest.
Simone, Veronica De; Caccavo, Diego; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters Book Chapter
In: Kyzas, George (Ed.): Chapter 5, IntechOpen, 2018, ISBN: 978-1-78984-308-8.
Abstract | Links | BibTeX | Tags: Granulation, HPMC, Mathematical modeling
@inbook{Simone}2018c,
title = {Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters},
author = {Veronica {De Simone} and Diego Caccavo and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
editor = {George Kyzas},
url = {https://www.intechopen.com/books/granularity-in-materials-science/inside-the-phenomenological-aspects-of-wet-granulation-role-of-process-parameters},
doi = {10.5772/intechopen.79840},
isbn = {978-1-78984-308-8},
year = {2018},
date = {2018-10-24},
publisher = {IntechOpen},
chapter = {5},
abstract = {Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.},
keywords = {Granulation, HPMC, Mathematical modeling},
pubstate = {published},
tppubtype = {inbook}
}
Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.
2017
Caccavo, Diego; Cascone, Sara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela
HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture Journal Article
In: Chemical Engineering Communications, vol. 204, no. 12, pp. 1333-1340, 2017, ISSN: 0098-6445.
Abstract | Links | BibTeX | Tags: Granulation, HPMC
@article{Caccavo2017b,
title = {HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture},
author = {Diego Caccavo and Sara Cascone and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398},
doi = {10.1080/00986445.2017.1362398 },
issn = {0098-6445},
year = {2017},
date = {2017-12-01},
journal = {Chemical Engineering Communications},
volume = {204},
number = {12},
pages = {1333-1340},
abstract = {One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.},
keywords = {Granulation, HPMC},
pubstate = {published},
tppubtype = {article}
}
One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.
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.
Abstract | Links | BibTeX | Tags: Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling
@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}
}
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.
Simone, Veronica De; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Central Composite Design in HPMC granulation and correlations between product properties and process parameters Journal Article
In: New Journal of Chemistry, vol. 41, no. 14, pp. 6504-6513, 2017.
Abstract | Links | BibTeX | Tags: Granulation, HPMC
@article{Simone}2017,
title = {Central Composite Design in HPMC granulation and correlations between product properties and process parameters},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ01280B#!divAbstract},
doi = {10.1039/C7NJ01280B},
year = {2017},
date = {2017-07-21},
journal = {New Journal of Chemistry},
volume = {41},
number = {14},
pages = {6504-6513},
abstract = {Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.},
keywords = {Granulation, HPMC},
pubstate = {published},
tppubtype = {article}
}
Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.
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.
Abstract | Links | BibTeX | Tags: HPMC, Hydrogel Characterization, Texture analysis, Water content
@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 = {HPMC, Hydrogel Characterization, Texture analysis, Water content},
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
Lamberti, Gaetano
Parametric simulation of drug release from hydrogel-based matrices Journal Article
In: Journal of Pharmacy and Pharmacology, vol. 64, no. 1, pp. 48–51, 2012, ISSN: 00223573.
Abstract | Links | BibTeX | Tags: drug release, FEM, HPMC, Hydrogels, modelling
@article{Lamberti2012,
title = {Parametric simulation of drug release from hydrogel-based matrices},
author = { Gaetano Lamberti},
url = {http://doi.wiley.com/10.1111/j.2042-7158.2011.01373.x},
doi = {10.1111/j.2042-7158.2011.01373.x},
issn = {00223573},
year = {2012},
date = {2012-01-01},
journal = {Journal of Pharmacy and Pharmacology},
volume = {64},
number = {1},
pages = {48--51},
publisher = {Blackwell Publishing Ltd},
abstract = {Objectives In this work a model recently proposed to describe the drug release from hydrogel-based matrices was applied to describe the fractional drug release from matrices based on hydroxypropylmethylcellulose (HPMC) and diclofenac. Methods The model, firstly proposed to describe the behaviour of systems based on HPMC and theophylline and a single set of preparation variables, is based on mass balances and transport phenomena evaluation and it was solved by an FEM-based numerical code. The experimental data on the HPMC\textendashdiclofenac matrices, taken from literature, have been obtained by varying the drug loading ratio, the compression force, the powder size of both the drug and the polymer. Key findings A good agreement between experimental data and model predictions, as calculated in the present work, was obtained without the use of any adjustable parameters. Conclusions The predictive nature of the model has been confirmed, even changing the drug molecule and other preparative parameters.},
keywords = {drug release, FEM, HPMC, Hydrogels, modelling},
pubstate = {published},
tppubtype = {article}
}
Objectives In this work a model recently proposed to describe the drug release from hydrogel-based matrices was applied to describe the fractional drug release from matrices based on hydroxypropylmethylcellulose (HPMC) and diclofenac. Methods The model, firstly proposed to describe the behaviour of systems based on HPMC and theophylline and a single set of preparation variables, is based on mass balances and transport phenomena evaluation and it was solved by an FEM-based numerical code. The experimental data on the HPMC–diclofenac matrices, taken from literature, have been obtained by varying the drug loading ratio, the compression force, the powder size of both the drug and the polymer. Key findings A good agreement between experimental data and model predictions, as calculated in the present work, was obtained without the use of any adjustable parameters. Conclusions The predictive nature of the model has been confirmed, even changing the drug molecule and other preparative parameters.
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.
Abstract | Links | BibTeX | Tags: Diffusion, drug release, HPMC, Hydrogel Characterization, swellable hydrogels, Theophylline
@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 = {Diffusion, drug release, HPMC, Hydrogel Characterization, swellable hydrogels, Theophylline},
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.
Abstract | Links | BibTeX | Tags: Erosion, Extended release, HPMC, Hydrogel Characterization, Swelling, Water diffusion
@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 = {Erosion, Extended release, HPMC, Hydrogel Characterization, Swelling, Water diffusion},
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.
2008
Reverchon, Ernesto; Lamberti, Gaetano; Antonacci, A
Supercritical fluid assisted production of HPMC composite microparticles Journal Article
In: The Journal of Supercritical Fluids, vol. 46, no. 2, pp. 185–196, 2008, ISSN: 08968446.
Abstract | Links | BibTeX | Tags: Ampicillin trihydrate, Drug controlled release, HPMC, Supercritical Assisted Atomization
@article{Reverchon2008,
title = {Supercritical fluid assisted production of HPMC composite microparticles},
author = { Ernesto Reverchon and Gaetano Lamberti and A Antonacci},
url = {http://www.sciencedirect.com/science/article/pii/S0896844608001319},
doi = {10.1016/j.supflu.2008.04.010},
issn = {08968446},
year = {2008},
date = {2008-09-01},
journal = {The Journal of Supercritical Fluids},
volume = {46},
number = {2},
pages = {185--196},
abstract = {Supercritical fluid technology has recently been proposed in literature to obtain drug controlled release systems as alternative to conventional techniques. In this work, the Supercritical Assisted Atomization (SAA) is proposed to produce hydroxypropyl methylcellulose (HPMC) based composite microparticles using ampicillin trihydrate as model drug. Successful micronization of HPMC alone and, then, coprecipitation of HPMC and ampicillin were obtained using a buffer solution as solvent. Well-defined micrometric particles with spherical or “doughnut-like” morphology were produced in both cases, with a sharp particle size distribution: diameters ranged between about 0.05 and 5.20$mu$m. SAA composite microparticles were characterized by differential scanning calorimetry (DSC), Scanning electronic microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) and UV\textendashvis analysis. A solid solution of HPMC and ampicillin was produced; a stabilizing effect of the polymer on the drug was observed, resulting in the protection of ampicillin from thermal degradation. Coprecipitates were produced at different drug/polymer ratios and two kinds of formulations for oral drug delivery were explored to verify ampicillin controlled release from HPMC: tablets and gelatine capsules of coprecipitated microparticles. Tablets released 97% of AMP in more than 72h, allowing a slower drug release than capsules, that released 100% of AMP in 8h. Drug release mechanisms characteristic of swelling-controlled systems were observed, with ampicillin release rate dominated by the erosion of HPMC matrix.},
keywords = {Ampicillin trihydrate, Drug controlled release, HPMC, Supercritical Assisted Atomization},
pubstate = {published},
tppubtype = {article}
}
Supercritical fluid technology has recently been proposed in literature to obtain drug controlled release systems as alternative to conventional techniques. In this work, the Supercritical Assisted Atomization (SAA) is proposed to produce hydroxypropyl methylcellulose (HPMC) based composite microparticles using ampicillin trihydrate as model drug. Successful micronization of HPMC alone and, then, coprecipitation of HPMC and ampicillin were obtained using a buffer solution as solvent. Well-defined micrometric particles with spherical or “doughnut-like” morphology were produced in both cases, with a sharp particle size distribution: diameters ranged between about 0.05 and 5.20$mu$m. SAA composite microparticles were characterized by differential scanning calorimetry (DSC), Scanning electronic microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) and UV–vis analysis. A solid solution of HPMC and ampicillin was produced; a stabilizing effect of the polymer on the drug was observed, resulting in the protection of ampicillin from thermal degradation. Coprecipitates were produced at different drug/polymer ratios and two kinds of formulations for oral drug delivery were explored to verify ampicillin controlled release from HPMC: tablets and gelatine capsules of coprecipitated microparticles. Tablets released 97% of AMP in more than 72h, allowing a slower drug release than capsules, that released 100% of AMP in 8h. Drug release mechanisms characteristic of swelling-controlled systems were observed, with ampicillin release rate dominated by the erosion of HPMC matrix.
2007
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.
Abstract | Links | BibTeX | Tags: Controlled drug release, Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Swelling
@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}
}
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.