Enhancing Bioequivalence Predictions with PAMPA Dissolution Using Formulations of Telmisartan

Abstract

Traditionally, the pilot bioequivalence study is a generalpractice for generic drug development. However, due to its difficulty in differentiating the variation between subject and drug formulation for bioequivalence results. A new instrument called PAMPA Dissolution is proposed in this study to improve the correlation between in vitro and in vivo absorption forbioequivalence study. PAMPA Dissolution allows for the simultaneous measurement of drug dissolution (Cb) and permeation (Pe), two key parameters in oral drug absorption according to the validated equation F (drug absorbed) = Cb*Pe*Area. The use of Parallel Artificial Membrane Permeability Assay (PAMPA) eliminates the concern of subject variation. Biorelevant media further allows this device to simulate in vivo conditions closely. Brand and generic formulations of 40 mg telmisartan tablets were used in various studies to demonstrate the potential of PAMPA Dissolution in generic drug development. Bioequivalence predictions between brand and generic telmisartan from PAMPA Dissolution produced avalue（test/reference）for Cmax of 86.3% and a value for AUC of 91.4%, indicating that PAMPA Dissolution predictions conform with bioequivalence requirements. Other parameters such as stirring at different speeds and phospholipids concentrations for PAMPA are also included for optimal performance of the system. Based on these data, the PAMPA Dissolution system is reproducible, precise, and can therefore be applied in predicting bioequivalence study.