Development and validation of discriminating method of dissolution for fosamprenavir tablets based on in vivo data.

摘要

The aim of this work is to develop and validate a dissolution test for fosamprenavir tablets (Telzir((R))) based on in vivo data. The appropriate conditions were determined after testing sink conditions in dissolution medium, rotation speed and stability of the drug. In vivo release profiles were obtained from the literature. The fraction (and percentage) of dose absorbed (FA) was calculated by deconvolution, using the Wagner-Nelson method. For this formulation, the best dissolution conditions were achieved using a USP apparatus 1 900 ml of medium containing HCl 0.01 M at a rotation speed of 75 rpm. Under these conditions a significant linear relationship between fraction of drug absorbed versus dissolved was obtained (R(2)=0.984) and a level-A IVIVC was established. The in vitro dissolution samples were analyzed using a HPLC method and the validation was performed according to USP protocol. The method showed accuracy, precision, linearity and specificity within the acceptable range. The discriminatory power of the dissolution method was challenged. The kinetics of dissolution was determined using model-dependent methods. The dissolution profiles were best described by the Hixson-Crowell model. The dissolution test was validated and could be applied to evaluate the dissolution profile of fosamprenavir tablets.