2020
|
De Piano, Raffaella ; Caccavo, Diego; Cascone, Sara; Festa, Caterina; Lamberti, Gaetano; Barba, Anna Angela Drug release from hydrogel-based matrix systems partially coated: experiments and modeling Journal Article Journal of Drug Delivery Science and Technology, 2020. Abstract | Links | BibTeX | Tags: drug release, Modeling, Tablets, Theophylline @article{Piano}2020,
title = {Drug release from hydrogel-based matrix systems partially coated: experiments and modeling},
author = {Raffaella {De Piano} and Diego Caccavo and Sara Cascone and Caterina Festa and Gaetano Lamberti and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720314350?via%3Dihub},
doi = {10.1016/j.jddst.2020.102146},
year = {2020},
date = {2020-10-07},
journal = {Journal of Drug Delivery Science and Technology},
abstract = {Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.},
keywords = {drug release, Modeling, Tablets, Theophylline},
pubstate = {published},
tppubtype = {article}
}
Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics. |
2017
|
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 International Journal of Pharmaceutics, 528 (1-2), pp. 345-353, 2017, ISSN: 0378-5173. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization @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 = {Drug Delivery Systems, drug release, Hydrogel Characterization},
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 British Journal of Pharmacology, 174 (12), pp. 1797–1809 , 2017, ISBN: 1476-5381. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling @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}
}
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. |
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 International journal of pharmaceutics, 407 (1-2), pp. 78–86, 2011, ISSN: 1873-3476. Abstract | Links | BibTeX | Tags: drug release, Hydrogel Modeling, Hydrogels, Mathematical modeling, Swelling; Erosion @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}
}
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. |
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 Journal of Pharmaceutical Sciences, 98 (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 A general code to predict the drug release kinetics from different shaped matrices. Journal Article European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 36 (2-3), pp. 359–68, 2009, ISSN: 1879-0720. Abstract | Links | BibTeX | Tags: drug release, Hydrogel Modeling, Matrix geometry, Modeling @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}
}
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. |
Associate Professor SSD ING-IND 25 (DIFARMA)
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