Development of a Two-Compartment System In vitro Dissolution Test and Correlation with In vivo Pharmacokinetic Studies for Celecoxib.

The objective of this study was to develop a novel open-mode two-compartment system dissolution apparatus to simulate the dissolution and absorption of poorly soluble drugs and to establish an in vitro-in vivo correlation (IVIVC). Celecoxib (CEB) was selected as a model drug, and in vitro dissolution was performed using the novel dissolution apparatus with acetate buffers at pH 4.5 containing Tween 80 (0.15%, w/v), at a flow rate of 30 mL/min and an agitation rate of 50 rpm. Cumulative release of all formulations was incomplete at approximately 70-80%, which likely reflected in vivo dissolution. Corresponding pharmacokinetic studies were performed in which twelve healthy male subjects from two bioequivalence studies received either one immediate release (IR) dose of the test (test 1 or test 2) or the reference formulation (Celebrex®, 200 mg). Individual plasma profiles of the formulations were deconvoluted via the Wanger-Nelson method to obtain the mean absorption fractions. A level A correlation was successfully developed with a good R2. The Weibull equation was used to describe the in vitro dissolution and in vivo absorption kinetics. In vitro dissolution correlated with in vivo absorption was applied successfully to predict the in vivo plasma concentrations-time profiles of the CEB formulations. Compared with conventional methods, the novel dissolution device showed great potential for discriminating the dissolution between formulations and generic drugs, which may provide a tool for making in vivo predictions for next bioequivalence trials.