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

Abstract

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.

Formulation and In Vitro and In Vivo Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration

“…Changing the drug-lipid ratio from 1:3 to 1:6 resulted in a significant decrease in %TBS released after 8, 12, and 24 h (P<0.0001). This agrees with previously reported results [32,33]. The authors reported that increasing the hydrophobic content of the matrix significantly reduced the rate and extent of drug release, as a result of increased drug diffusion path length, the decrease in the total porosity of the matrices, and the negative effect of hydrophobic matrix against the penetration of the aqueous dissolution medium.…”

Bioenhanced sublingual tablet of drug with limited permeability using novel surfactant binder and microencapsulated polysorbate: In vitro/in vivo evaluation

“…The inclusion of the confidence interval within 0.8-1.25 was taken as a demonstration of bioequivalence [21]. The nonparametric Kruskall-Wallis test was used to compare the medians of t max for treatments A and B.…”

Hot-melts in buccoadhesive patches: An approach for bioavailability enhancement of highly-metabolized drugs with short elimination half-life

“…The molten mass was rapidly cooled over an ice bath and allowed to solidify. The solidified mass was pulverized in a mortar then sieved through 0.5 lm sieve [2,4].…”

“…The drug particles were embedded in the lipophilic Compritol which decreased the penetration of the dissolution medium to the drug, resulting in a decreased dissolution [4,6]. So TIZ Compritol-based hot-melts added a second control on the release of TIZ from the patch, after the control exerted by the patch gel itself.…”

“…Hot-melts can be used as a maneuver to control drug release if prepared with a water insoluble carrier, such as Compritol 888 ATO. Compritol has waxy lipophilic properties that make it an ideal retardant carrier for sustained release of water soluble drugs [4].…”