2016
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Cascone, Sara; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe; d'Amore, Matteo; Barba, Anna Angela Gastrointestinal behavior and ADME phenomena: I. In vitro simulation Journal Article Journal of Drug Delivery Science and Technology, 35 , pp. 272-283, 2016, ISSN: 1773-2247. Abstract | Links | BibTeX | Tags: Biodistribution, In vitro, Pharmacokinetics @article{Cascone2016,
title = {Gastrointestinal behavior and ADME phenomena: I. In vitro simulation},
author = {Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Matteo d'Amore and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/pii/S1773224716302659
},
doi = {10.1016/j.jddst.2016.08.002},
issn = {1773-2247},
year = {2016},
date = {2016-10-01},
journal = {Journal of Drug Delivery Science and Technology},
volume = {35},
pages = {272-283},
abstract = {The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals.
This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed.},
keywords = {Biodistribution, In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals.
This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed. |
Piazza, Ornella; Cascone, Sara; Sessa, Linda; De Robertis, Edoardo ; Lamberti, Gaetano The effect of liver esterases and temperature on remifentanil degradation in vitro Journal Article International Journal of Pharmaceutics, 510 (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. |
2015
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Cascone, Sara; Barba, Anna Angela; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe Bioaccessibility of active principles: an in-vitro reproduction of human physiology Inproceedings Proccedings of 4th International Conference on Food Digestion, pp. 1–1, 4th International Conference on Food Digestion, Naples, Italy, 2015. BibTeX | Tags: In vitro, Pharmacokinetics @inproceedings{cascone2015b,
title = {Bioaccessibility of active principles: an in-vitro reproduction of human physiology},
author = { Sara Cascone and Anna Angela Barba and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio},
year = {2015},
date = {2015-03-01},
booktitle = {Proccedings of 4th International Conference on Food Digestion},
pages = {1--1},
publisher = {4th International Conference on Food Digestion},
address = {Naples, Italy},
keywords = {In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
|
2014
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Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela In-vitro models of the gastro-intestinal tract for pharmaceutical and nutritional purposes Inproceedings 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}
}
|
Cascone, Sara; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe; Barba, Anna Angela AN IN VITRO MODEL TO REPRODUCE THE MECHANICS AND THE ABSORPTION IN THE GASTROINTESTINAL TRACT Inproceedings 13th European Symposium on Controlled Drug Delivery, pp. 1–2, ESCDD 2014, Egmond aan Zee, The Netherlands, 2014. BibTeX | Tags: In vitro, Pharmacokinetics @inproceedings{s.2014-1,
title = {AN IN VITRO MODEL TO REPRODUCE THE MECHANICS AND THE ABSORPTION IN THE GASTROINTESTINAL TRACT},
author = { Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Anna Angela Barba},
year = {2014},
date = {2014-04-01},
booktitle = {13th European Symposium on Controlled Drug Delivery},
pages = {1--2},
publisher = {ESCDD 2014},
address = {Egmond aan Zee, The Netherlands},
keywords = {In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
|
Cascone, Sara; Barba, Anna Angela; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe In-vitro reproduction of human physiology involved in bioaccessibility of drugs and nutrients Inproceedings Proceedings of Conference of Food Engineering (CoFE), pp. 1–2, Conference of Food Engineering (CoFE), Omaha, Nebraska, 2014. BibTeX | Tags: In vitro, Pharmacokinetics @inproceedings{cascone2014b,
title = {In-vitro reproduction of human physiology involved in bioaccessibility of drugs and nutrients},
author = { Sara Cascone and Anna Angela Barba and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio},
year = {2014},
date = {2014-04-01},
booktitle = {Proceedings of Conference of Food Engineering (CoFE)},
pages = {1--2},
publisher = {Conference of Food Engineering (CoFE)},
address = {Omaha, Nebraska},
keywords = {In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
|
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe Simulation of gastrointestinal tract: mechanics and absorption Inproceedings Proceedings of PBP 2014, pp. 3–4, PBP 2014, Lisbon, Portugal, 2014. BibTeX | Tags: In vitro, Pharmacokinetics @inproceedings{s.2014-2,
title = {Simulation of gastrointestinal tract: mechanics and absorption},
author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio},
year = {2014},
date = {2014-03-01},
booktitle = {Proceedings of PBP 2014},
pages = {3--4},
publisher = {PBP 2014},
address = {Lisbon, Portugal},
keywords = {In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
|
2012
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Lamberti, Gaetano; Cascone, Sara; Iannaccone, Margherita; Titomanlio, Giuseppe In vitro simulation of drug intestinal absorption. Journal Article International journal of pharmaceutics, 439 (1-2), pp. 165–8, 2012, ISSN: 1873-3476. Abstract | Links | BibTeX | Tags: Controlled drug release, In vitro, Intestinal Absorption, Mass balance, Oral administration, Pharmacokinetics, Theophylline @article{Lamberti2012d,
title = {In vitro simulation of drug intestinal absorption.},
author = { Gaetano Lamberti and Sara Cascone and Margherita Iannaccone and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S0378517312009520},
doi = {10.1016/j.ijpharm.2012.10.012},
issn = {1873-3476},
year = {2012},
date = {2012-12-01},
journal = {International journal of pharmaceutics},
volume = {439},
number = {1-2},
pages = {165--8},
abstract = {In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids real behavior (the gastro intestinal lumen and the gastro intestinal circulatory system). The realized set-up was characterized in term of mass exchange characteristic, using the theophylline as the model drug, also with the aid of a simple mathematical model; then the release kinetics of a controlled release tablet was evaluated in the conventional test as well as in the novel simulator. The concentration of drug in the release compartment (which simulates the gastric lumen) was found lower in the novel simulator than in the traditional one.},
keywords = {Controlled drug release, In vitro, Intestinal Absorption, Mass balance, Oral administration, Pharmacokinetics, Theophylline},
pubstate = {published},
tppubtype = {article}
}
In this work, a simple set-up was designed, realized and tested to evaluate the effect of intestinal absorption on the in vitro drug release studies. The conventional USP-approved dissolution apparatus 2 was equipped with an hollow fibers filter, along with the necessary tubing and pumps, to simulate the two-fluids real behavior (the gastro intestinal lumen and the gastro intestinal circulatory system). The realized set-up was characterized in term of mass exchange characteristic, using the theophylline as the model drug, also with the aid of a simple mathematical model; then the release kinetics of a controlled release tablet was evaluated in the conventional test as well as in the novel simulator. The concentration of drug in the release compartment (which simulates the gastric lumen) was found lower in the novel simulator than in the traditional one. |
Cascone, Sara; Lamberti, Gaetano; Paolucci, Fabio; Titomanlio, Giuseppe In vitro and in silico approaches to reproduce pharmacokinetic relevant phenomena Inproceedings Proceedings of 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, pp. 1–2, PBP 2012, Istanbul, Turkey, 2012. BibTeX | Tags: In silico, In vitro, Pharmacokinetics @inproceedings{s.2012,
title = {In vitro and in silico approaches to reproduce pharmacokinetic relevant phenomena},
author = { Sara Cascone and Gaetano Lamberti and Fabio Paolucci and Giuseppe Titomanlio},
year = {2012},
date = {2012-03-01},
booktitle = {Proceedings of 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology},
pages = {1--2},
publisher = {PBP 2012},
address = {Istanbul, Turkey},
keywords = {In silico, In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
|
2011
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Cascone, Sara; Santis, Felice De; Lamberti, Gaetano; Titomanlio, Giuseppe The influence of dissolution conditions on the drug ADME phenomena. Journal Article European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V, 79 (2), pp. 382–91, 2011, ISSN: 1873-3441. Abstract | Links | BibTeX | Tags: ADME, Dissolution, Enteric coated, In silico, In vitro, Pharmacokinetic modeling, Pharmacokinetics @article{Cascone2011,
title = {The influence of dissolution conditions on the drug ADME phenomena.},
author = { Sara Cascone and Felice De Santis and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S093964111100141X},
doi = {10.1016/j.ejpb.2011.04.003},
issn = {1873-3441},
year = {2011},
date = {2011-10-01},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft f\"{u}r Pharmazeutische Verfahrenstechnik e.V},
volume = {79},
number = {2},
pages = {382--91},
abstract = {In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized.},
keywords = {ADME, Dissolution, Enteric coated, In silico, In vitro, Pharmacokinetic modeling, Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
In this work, a review of the apparatuses available to mimic what happens to a drug (or to foodstuffs) once ingested is presented. Similarly, a brief review of the models proposed to simulate the fate of a drug administered to a living body is reported. Then, the release kinetics of extended release of diclofenac from a commercial enteric-coated tablet was determined both in a conventional dissolution tester (USP Apparatus 2, Method A) as well as in an apparatus modified to reproduce a given pH evolution, closer to the real one than the one suggested by USP. The two experimental release profiles were reported and discussed; therefore, they were adopted as input functions for a previously proposed pharmacokinetic model. The obtained evolutions with time of plasma concentration were presented and used to assess the effectiveness of the commercial pharmaceutical products. The importance of a correct in vitro simulation for the design of pharmaceutical dosage systems was thus emphasized. |
Full Professor SSD ING-IND/24 (DIIN)
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