Improve Bioequivalence predictions with PAMPA Dissolution using Etoricoxib and five other Drug Formulations

Abstract

In the generic drug formulation development, pilot bioequivalence (BE) study with a small group of subjects is the current practice for oral formulation prediction. However, due to the difficulty in differentiating the variation between subject and drug formulation with the current BE practice，a new instrument called PAMPA Dissolution is proposed to eliminate the subjects variation and to enhance the correlation between in vitro to in vivo absorption in BE study. PAMPA Dissolution simultaneously measures drug dissolution (Cb) and permeation (Pe), following the validated oral drug absorption equation F (drug absorbed) = Cb*Pe*Area. The use of biorelevant media further allows this device to mimic in vivo conditions closely. Formulations of 60 mg etoricoxib tablets were studied to verify system reproducibility and BE prediction to demonstrate the potential of PAMPA Dissolution in generic drug development. The BE predictions between generic and brand etoricoxib tablets (test/reference) from this system produced a Cmax value of 99.0% and AUC value of 99.1%, indicating that PAMPA Dissolution predictions conform with bioequivalence results. Other oral formulations of valsartan/hydrochlorothiazide, ezetimibe, telmisartan, and amlodipine were also tested for their permeation (Pe) by PAMPA Dissolution. Results of drug permeation compared to the literature values indicates that the PAMPA Dissolution is reliable and precise in formulation development.