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Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.
Eur J Pharm Biopharm. 2014 Jul; 87(2):236-43.EJ

Abstract

The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms.

Authors+Show Affiliations

Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.SocraTec R&D GmbH, Oberursel, Germany.Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany. Electronic address: dressman@em.uni-frankfurt.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24462791

Citation

Kambayashi, Atsushi, et al. "Predicting the Oral Pharmacokinetic Profiles of Multiple-unit (pellet) Dosage Forms Using a Modeling and Simulation Approach Coupled With Biorelevant Dissolution Testing: Case Example Diclofenac Sodium." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 87, no. 2, 2014, pp. 236-43.
Kambayashi A, Blume H, Dressman JB. Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium. Eur J Pharm Biopharm. 2014;87(2):236-43.
Kambayashi, A., Blume, H., & Dressman, J. B. (2014). Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 87(2), 236-43. https://doi.org/10.1016/j.ejpb.2014.01.007
Kambayashi A, Blume H, Dressman JB. Predicting the Oral Pharmacokinetic Profiles of Multiple-unit (pellet) Dosage Forms Using a Modeling and Simulation Approach Coupled With Biorelevant Dissolution Testing: Case Example Diclofenac Sodium. Eur J Pharm Biopharm. 2014;87(2):236-43. PubMed PMID: 24462791.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium. AU - Kambayashi,Atsushi, AU - Blume,Henning, AU - Dressman,Jennifer B, Y1 - 2014/01/23/ PY - 2013/09/27/received PY - 2014/01/10/revised PY - 2014/01/15/accepted PY - 2014/1/28/entrez PY - 2014/1/28/pubmed PY - 2015/2/3/medline KW - Biorelevant media KW - Diclofenac KW - Enteric coated pellet KW - Modeling and simulation KW - Multiple units dosage form KW - Oral administration KW - Pharmacokinetics SP - 236 EP - 43 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 87 IS - 2 N2 - The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/24462791/Predicting_the_oral_pharmacokinetic_profiles_of_multiple_unit__pellet__dosage_forms_using_a_modeling_and_simulation_approach_coupled_with_biorelevant_dissolution_testing:_case_example_diclofenac_sodium_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(14)00008-3 DB - PRIME DP - Unbound Medicine ER -