LAUSR

PURPOSE The aim of this study was to predict the plasma concentrations of acebutolol tablets with different dissolution profiles using computer modelling and evaluating whether they are bioequivalent using simulated population studies. METHODS The dissolution behaviour of acebutolol was studied in the USP Apparatus-II using different dissolution media for pH 1.2, 4.5, and 6.8 at 37 ± 0.5 °C. The obtained dissolution data, as well as plasma concentration-time data of the reference product from the literature were used as inputs to build pharmacokinetic model of acebutolol within GastroPlusTM software (version 9.7, Simulations Plus Inc., Lancaster, CA, USA) to simulate the in vivo profiles of the drug. RESULTS The dissolution profiles of the reference product Sectral® 400 mg tablets and a locally produced generic product were > 85% in 15 min in three dissolution media. Simulation results demonstrated that the brand and generic products would show the same in vivo performance. Population simulation results of the ln-transformed 90% confidence interval for the ratio of Cmax, AUC0-t and AUC0-inf values for the two products were within the 80-125% interval, showing to be bioequivalent. Conclusion Based on the in vitro results combined with in silico simulations using GastroPlusTM, a biowaiver for immediate release acebutolol tablets is justified. Furthermore, computer modelling has shown to be a very intersting tool to prove the bioequivalence for these products.