Development and validation of an in vitro-in vivo correlation for buspirone hydrochloride extended release tablets.

The aim of this study was to develop an in-vitro-in-vivo correlation (IVIVC) for two buspirone hydrochloride extended release formulations and to compare their plasma concentrations over time with the commercially available immediate release (IR) tablets. In vitro release rate data were obtained for each formulation using the USP Apparatus 2, paddle stirrer at 50 and 100 rpm in 0.1 M HCl and pH 6.8 phosphate buffer. A three-way crossover study in 18 healthy subjects studied a 30 mg "Fast" (12 h) and 30 mg "Slow" (24 h) formulation of buspirone hydrochloride given once a day, and 2x15 mg immediate release tablets dosed at a 12 h interval. The similarity factor (f(2)) was used to analyze the dissolution data. A linear correlation model was developed using percent absorbed data and percent dissolved data from the two formulations. Predicted buspirone hydrochloride concentrations were obtained by use of a curve fitting equation for the immediate release data to determine the volume of distribution and fraction absorbed constants. Prediction errors were estimated for C(max) and area under the curve (AUC) to determine the validity of the correlation. pH 6.8 at 50 rpm was found to be the most discriminating dissolution method. Linear regression analyses of the mean percentage of dose absorbed versus the mean in vitro release resulted in a significant correlation (r(2)>0.95) for the two formulations. An average percent prediction error for C(max) was -0.16%, but was 16.1%, for the AUCs of the two formulations.

RCT Entities:   Population Interventions Outcomes