The publications of the members of the research group.
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
In: Chemical Engineering Science, vol. 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.
2017
Cascone, Sara; Santis, Felice De; Lamberti, Gaetano
Mimicking the contractions of a human stomach and their effect on pharmaceuticals Journal Article
In: Journal of Drug Delivery Science and Technology, vol. 41, pp. 454-461, 2017, ISSN: 1773-2247.
Abstract | Links | BibTeX | Tags: Pharmacokinetics
@article{Cascone2017b,
title = {Mimicking the contractions of a human stomach and their effect on pharmaceuticals},
author = {Sara Cascone and Felice {De Santis} and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S1773224717305907},
doi = {10.1016/j.jddst.2017.09.008},
issn = {1773-2247},
year = {2017},
date = {2017-10-01},
journal = {Journal of Drug Delivery Science and Technology},
volume = {41},
pages = {454-461},
abstract = {The prediction of the drug’s fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body.},
keywords = {Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
The prediction of the drug’s fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body.
2016
Piazza, Ornella; Cascone, Sara; Sessa, Linda; Robertis, Edoardo De; Lamberti, Gaetano
The effect of liver esterases and temperature on remifentanil degradation in vitro Journal Article
In: International Journal of Pharmaceutics, vol. 510, no. 1, pp. 359–364, 2016.
Abstract | Links | BibTeX | Tags: In vitro, Pharmacokinetics
@article{Piazza2016b,
title = {The effect of liver esterases and temperature on remifentanil degradation in vitro},
author = {Ornella Piazza and Sara Cascone and Linda Sessa and Edoardo {De Robertis} and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0378517316305191},
doi = {10.1016/j.ijpharm.2016.06.043},
year = {2016},
date = {2016-07-04},
journal = {International Journal of Pharmaceutics},
volume = {510},
number = {1},
pages = {359\textendash364},
abstract = {Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.},
keywords = {In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.
2014
Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela
In-vitro models of the gastro-intestinal tract for pharmaceutical and nutritional purposes Proceedings Article
In: Proceedings of CHISA 2014/PRES 2014, pp. 2–2, CHISA 2014, Prague, Czech Republic, 2014.
BibTeX | Tags: In vitro, Pharmacokinetics
@inproceedings{s.2014-4,
title = {In-vitro models of the gastro-intestinal tract for pharmaceutical and nutritional purposes},
author = { Sara Cascone and Diego Caccavo and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba},
year = {2014},
date = {2014-08-01},
booktitle = {Proceedings of CHISA 2014/PRES 2014},
pages = {2--2},
publisher = {CHISA 2014},
address = {Prague, Czech Republic},
keywords = {In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
Cont, Renzo Del; Abrami, Michela; Hasa, Dritan; Perissutti, Beatrice; Voinovich, Dario; Barba, Anna Angela; Lamberti, Gaetano; Grassi, Gabriele; Colombo, Italo; Manca, Davide; Grassi, Mario
A physiologically oriented mathematical model for the description of in vivo drug release and absorption Journal Article
In: ADMET & DMPK, vol. 2, no. 2, pp. 80–97, 2014, ISSN: 1848-7718.
Abstract | Links | BibTeX | Tags: In silico, Pharmacokinetics
@article{del2014physiologically,
title = {A physiologically oriented mathematical model for the description of in vivo drug release and absorption},
author = {Renzo {Del Cont} and Michela Abrami and Dritan Hasa and Beatrice Perissutti and Dario Voinovich and Anna Angela Barba and Gaetano Lamberti and Gabriele Grassi and Italo Colombo and Davide Manca and Mario Grassi},
url = {http://pub.iapchem.org/ojs/index.php/admet/article/view/34},
doi = {10.5599/admet.2.2.34},
issn = {1848-7718},
year = {2014},
date = {2014-07-01},
journal = {ADMET \& DMPK},
volume = {2},
number = {2},
pages = {80--97},
abstract = {This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.},
keywords = {In silico, Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.