Optimization and in vivo pharmacokinetic study of a novel controlled release venlafaxine hydrochloride three-layer tablet.
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.
Aboelwafa
Ahmed A
AA
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini street, 11562, Cairo, Egypt. aaboelwafa@hotmail.com
Basalious
Emad B
EB
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000737:chemistry / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003511:Cyclohexanols / Q000737:chemistry* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D013607:Tablets / Q000138:chemical synthesis*; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D013607:Tablets; D000069470:Venlafaxine Hydrochloride