In vitro-in vivo correlation of efavirenz tablets using GastroPlus®.
The aim of the present work was to use GastroPlus™ software for the prediction of pharmacokinetic profiles and in vitro-in vivo correlation (IVIVC) as tools to optimize the development of new generic medications. GastroPlus™ was used to simulate the gastrointestinal compartment and was based on the advanced compartmental absorption and transit model. Powder dissolution and efavirenz tablet dissolution studies were carried out to generate data from which correlation was established. The simulated plasma profile, based on the physicochemical properties of efavirenz, was almost identical to that observed in vivo for biobatches A and B. A level A IVIVC was established for the dissolution method obtained for the generic candidate using the Wagner-Nelson (r (2) = 0.85) and for Loo-Riegelman models (r(2) = 0.92). The percentage of fraction absorbed indicated that 0.5% sodium lauryl sulfate may be considered a biorelevant dissolution medium for efavirenz tablets. The simulation of gastrointestinal bioavailability and IVIVC obtained from immediate-release tablet formulations suggests that GastroPlus™ is a valuable in silico method for IVIVC and for studies directed at developing formulations of class II drugs.
Faculty of Pharmacy, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bloco Bss 15, Cidade Universitária, CEP 21.941-902, Rio de Janeiro, RJ, Brazil.
Thiago da Silva
Tda S
Honório
Eduardo Costa
EC
Pinto
Helvécio Vinicius A
HV
Rocha
Valeria Sant'Anna Dantas
VS
Esteves
Tereza Cristina
TC
dos Santos
Helena Carla Rangel
HC
Castro
Carlos Rangel
CR
Rodrigues
Valeria Pereira
VP
de Sousa
Lucio Mendes
LM
Cabral
D000480:Alkynes; D048588:Benzoxazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D003521:Cyclopropanes; D066298:In Vitro Techniques; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D013607:Tablets; D013810:Therapeutic Equivalency
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; C098320:efavirenz