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A physiologically-based drug absorption modeling for orally disintegrating tablets.
Eur J Pharm Biopharm. 2020 Jul; 152:1-9.EJ

Abstract

The aim of this research was to simulate oral pharmacokinetic (PK) profiles of atorvastatin from orally disintegrating tablets (ODTs) dosed without water ingestion in fasted humans. The in vitro dissolution profiles of three different formulations of ODTs were evaluated with fasted state biorelevant media using a paddle dissolution apparatus, and the results were coupled with an in silico model to simulate the in vivo oral PK profiles of ODTs following administration to humans. Since the dissolution rates of the ODTs in the intestinal medium (FaSSIF-V2) were highly affected by pre-exposure of the tablets to the stomach medium (FaSSGF), the simulation model took account of the relationship between the gastric emptying time and the dissolution performance of the tablets in the small intestine. The ODTs were formulated with drug-containing pellets. After oral dosing of the ODTs without water ingestion, gastric emptying of the pellets was assumed to follow first order kinetics. Thus, rate constants ranging between 0.69 and 8.3 h-1 were applied in the PK simulations. The simulation model was built using Stella Professional® software. The results of the PK simulations suggest that the plasma concentration profiles of the ODTs can be described using the prediction model, but that different gastric emptying parameters for each ODT formulation are needed in humans.

Authors+Show Affiliations

Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan. Electronic address: atsushi.kambayashi@astellas.com.Pharmaceutical Research and Technology Labs, Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32371153

Citation

Kambayashi, Atsushi, and Tsuyoshi Kiyota. "A Physiologically-based Drug Absorption Modeling for Orally Disintegrating Tablets." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 152, 2020, pp. 1-9.
Kambayashi A, Kiyota T. A physiologically-based drug absorption modeling for orally disintegrating tablets. Eur J Pharm Biopharm. 2020;152:1-9.
Kambayashi, A., & Kiyota, T. (2020). A physiologically-based drug absorption modeling for orally disintegrating tablets. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 152, 1-9. https://doi.org/10.1016/j.ejpb.2020.04.018
Kambayashi A, Kiyota T. A Physiologically-based Drug Absorption Modeling for Orally Disintegrating Tablets. Eur J Pharm Biopharm. 2020;152:1-9. PubMed PMID: 32371153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A physiologically-based drug absorption modeling for orally disintegrating tablets. AU - Kambayashi,Atsushi, AU - Kiyota,Tsuyoshi, Y1 - 2020/05/01/ PY - 2020/02/29/received PY - 2020/04/26/revised PY - 2020/04/26/accepted PY - 2020/5/7/pubmed PY - 2020/5/7/medline PY - 2020/5/7/entrez KW - Atorvastatin KW - In silico modeling and simulation KW - In vitro biorelevant dissolution KW - Oral drug absorption KW - Orally disintegrating tablets KW - Orodispersible tablets KW - Pharmacokinetics SP - 1 EP - 9 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 152 N2 - The aim of this research was to simulate oral pharmacokinetic (PK) profiles of atorvastatin from orally disintegrating tablets (ODTs) dosed without water ingestion in fasted humans. The in vitro dissolution profiles of three different formulations of ODTs were evaluated with fasted state biorelevant media using a paddle dissolution apparatus, and the results were coupled with an in silico model to simulate the in vivo oral PK profiles of ODTs following administration to humans. Since the dissolution rates of the ODTs in the intestinal medium (FaSSIF-V2) were highly affected by pre-exposure of the tablets to the stomach medium (FaSSGF), the simulation model took account of the relationship between the gastric emptying time and the dissolution performance of the tablets in the small intestine. The ODTs were formulated with drug-containing pellets. After oral dosing of the ODTs without water ingestion, gastric emptying of the pellets was assumed to follow first order kinetics. Thus, rate constants ranging between 0.69 and 8.3 h-1 were applied in the PK simulations. The simulation model was built using Stella Professional® software. The results of the PK simulations suggest that the plasma concentration profiles of the ODTs can be described using the prediction model, but that different gastric emptying parameters for each ODT formulation are needed in humans. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/32371153/A_physiologically-based_drug_absorption_modeling_for_orally_disintegrating_tablets L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(20)30115-6 DB - PRIME DP - Unbound Medicine ER -
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