2023
|
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 Chemical Engineering Science, 267 , 2023. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, Mathematical modeling, Pharmacokinetics @article{Caccavo2023,
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.sciencedirect.com/science/article/pii/S0009250922009563},
doi = {10.1016/j.ces.2022.118371},
year = {2023},
date = {2023-03-05},
journal = {Chemical Engineering Science},
volume = {267},
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 = {Drug Delivery Systems, Mathematical modeling, Pharmacokinetics},
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
|
Milocco, Alessio; Scuor, Nicola; Lughi, Vanni; Lamberti, Gaetano; Barba, Anna Angela; Divittorio, Rosario; Grassi, Gabriele; Perkan, Andrea; Grassi, Mario; Abrami, Michela Thermal gelation modeling of a pluronic-alginate blend following coronary angioplasty Journal Article Journal of Applied Polymer Science, 137 (25), pp. 10, 2020. Abstract | Links | BibTeX | Tags: alginate-pluronic, coronary angioplasty, Mathematical modeling, restenosis @article{Milocco2020,
title = {Thermal gelation modeling of a pluronic-alginate blend following coronary angioplasty },
author = {Alessio Milocco and Nicola Scuor and Vanni Lughi and Gaetano Lamberti and Anna Angela Barba and Rosario Divittorio and Gabriele Grassi and Andrea Perkan and Mario Grassi and Michela Abrami},
url = {https://onlinelibrary.wiley.com/doi/epdf/10.1002/app.48539},
doi = {10.1002/app.48539},
year = {2020},
date = {2020-07-05},
journal = {Journal of Applied Polymer Science},
volume = {137},
number = {25},
pages = {10},
abstract = {To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter. },
keywords = {alginate-pluronic, coronary angioplasty, Mathematical modeling, restenosis},
pubstate = {published},
tppubtype = {article}
}
To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter. |
2019
|
Barba, Anna Angela; Bochicchio, Sabrina; Dalmoro, Annalisa; Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano Polymeric and lipid-based systems for controlled drug release: an engineering point of view Book Chapter Grumezescu, Alexandru Mihai (Ed.): Chapter 10, pp. 267-304, Elsevier, 2019, ISBN: 978-0-12-816505-8. Abstract | Links | BibTeX | Tags: characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes @inbook{Barba2019c,
title = {Polymeric and lipid-based systems for controlled drug release: an engineering point of view},
author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Diego Caccavo and Sara Cascone and Gaetano Lamberti},
editor = {Alexandru Mihai Grumezescu},
url = {https://www.sciencedirect.com/science/article/pii/B9780128165058000138?via%3Dihub#kys0010},
doi = {10.1016/B978-0-12-816505-8.00013-8},
isbn = {978-0-12-816505-8},
year = {2019},
date = {2019-12-02},
pages = {267-304},
publisher = {Elsevier},
chapter = {10},
abstract = {Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view.
The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems’ preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared.},
keywords = {characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes},
pubstate = {published},
tppubtype = {inbook}
}
Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view.
The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems’ preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared. |
2018
|
De Simone, Veronica ; 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 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; 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 International Journal of Pharmaceutics, 528 (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. |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications Journal Article Natural Product Communications, 12 (6), pp. 867-871, 2017, ISSN: 1934-578X. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling @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}
}
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.
|
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. |
Professore Associato SSD ING-IND 25 (DIFARMA)
+39.089.969240
