In Vitro-In Vivo Correlation of Efavirenz Tablets Using GastroPlus (R)

作者：Honorio Thiago da Silva; Pinto Eduardo Costa; Rocha Helvecio Vinicius A; Dantas Esteves Valeria Sant' Anna; dos Santos Tereza Cristina; Rangel Castro Helena Carla; Rodrigues Carlos Rangel; de Sousa Valeria Pereira^*; Cabral Lucio Mendes

来源：AAPS PharmSciTech, 2013, 14(3): 1244-1254.

DOI：10.1208/s12249-013-0016-4

• bioavailability
• computational simulation
• efavirenz
• GastroPlus (TM)
• in vivo-in vitro correlation

The aim of the present work was to use GastroPlus (TM) 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 (TM) 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 (TM) is a valuable in silico method for IVIVC and for studies directed at developing formulations of class II drugs.

• 出版日期2013-9