In Vitro–In Vivo Correlation of Efavirenz Tablets Using GastroPlus

• Published in: AAPS PharmSciTech Vol. 14; no. 3; pp. 1244 - 1254
• Main Authors: Honório, Thiago da Silva, Pinto, Eduardo Costa, Rocha, Helvécio Vinicius A., Esteves, Valeria Sant’Anna Dantas, dos Santos, Tereza Cristina, Castro, Helena Carla Rangel, Rodrigues, Carlos Rangel, de Sousa, Valeria Pereira, Cabral, Lucio Mendes
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-09-2013
• Subjects: Benzoxazines - chemistry; Benzoxazines - pharmacokinetics; Benzoxazines - pharmacology; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedicine; Biotechnology; In Vitro Techniques; Pharmacology/Toxicology; Pharmacy; Research Article; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacokinetics; Reverse Transcriptase Inhibitors - pharmacology; Solubility; Tablets; Therapeutic Equivalency; computational simulation; GastroPlus; correlation; bioavailability; efavirenz
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-013-0016-4

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.