Le pubblicazioni dei componenti del gruppo di ricerca.
2024
Piano, Raffaella De; 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
In: Journal of Drug Delivery Science and Technology, vol. 61, no 102146, 2024, ISBN: 17732247.
Abstract | Links | BibTeX | Tags: drug release, Modeling, Tablets, Theophylline
@article{Piano}2024,
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.scopus.com/inward/record.uri?eid=2-s2.0-85092403044\&doi=10.1016%2fj.jddst.2020.102146\&partnerID=40\&md5=e519d84642480478a063b4c7b4e2832e},
doi = {10.1016/j.jddst.2020.102146},
isbn = {17732247},
year = {2024},
date = {2024-05-01},
journal = {Journal of Drug Delivery Science and Technology},
volume = {61},
number = {102146},
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.
Caccavo, Diego; Iannone, Marco; Barba, Anna Angela; Lamberti, Gaetano
Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets Journal Article
In: Chemical Engineering Science, vol. 267, no 118371, 2024, ISSN: 92509.
Abstract | Links | BibTeX | Tags: case study, drug release, in-vitro stomach
@article{Caccavo2024b,
title = {Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets},
author = {Diego Caccavo and Marco Iannone and Anna Angela Barba and Gaetano Lamberti},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145821046\&doi=10.1016%2fj.ces.2022.118371\&partnerID=40\&md5=d837f63862ad2ca8881845352400e79a},
doi = {10.1016/j.ces.2022.118371},
issn = {92509},
year = {2024},
date = {2024-03-05},
journal = {Chemical Engineering Science},
volume = {267},
number = {118371},
abstract = {The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.},
keywords = {case study, drug release, in-vitro stomach},
pubstate = {published},
tppubtype = {article}
}
The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.
2020
Piano, Raffaella De; 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
In: 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
In: International Journal of Pharmaceutics, vol. 528, no 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
In: British Journal of Pharmacology, vol. 174, no 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.
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.