Optimization and In vivo Pharmacokinetic Study of a Novel Controlled Release Venlafaxine Hydrochloride Three-Layer Tablet

Abstract

Several matrix tablet formulations (hydrophilic-based, wax-based, and three-layer tablets) were designed for controlling the release of the highly water soluble drug, venlafaxine hydrochloride (VenHCl) for once-daily administration. The three-layer tablets consist of non-swellable, compritol-based middle layers containing the drug to which hydrophilic top and bottom barrier layers were applied. A 2(3) full-factorial design was employed for optimization and to explore the effect of different variables on the release rate of the drug from the three-layer tablets. The optimized levels of each independent variable were based on the criterion of desirability. The calculated values of f(1) and f(2) were 4.131 and 79.356, respectively; indicating that the release profile of the optimized PEO layered tablet formulation is comparable to that of the target release model. The pharmacokinetic parameters of VenHCl from the optimized three-layer tablet was compared to the marketed extended release capsule as a reference in healthy human subjects using a randomized crossover design. In this study, the 90% confidence interval for AUC(0-24) and AUC(0-∞) are within (0.8-1.25), which satisfied the bioequivalence criteria. It could be concluded that a promising once-daily extended-release three-layer tablet of the highly water soluble drug, VenHCl, was successfully designed.