An improved in vitro method for the evaluation of antacids with in vivo relevance

Abstract

An improved in vitro method for the evaluation of antacids for use with standard equipment is described. The method is a modification of an older method (RIGO method) and has in vivo relevance. The improved method uses USP dissolution test apparatus 2 with a stirring rate of 125 rpm in combination with a computerized automatic burette. The test solution is 250 ml 0.02 M HCl. A total of 20 min after addition of an antacid to the test solution titration starts at a constant speed of 2.0 ml/min 0.1 M HCl. The proposed acceptance criteria for a waiver for clinical studies are: pH after 4 min not less than 2.5 to ensure a rapid onset of effect, pH after 20 min not exceeding 7.0 to ensure that the pH in the stomach remains within physiological values, buffering capacity between pH 2.5 and 4.5 not less than 8 meq/dose and neutralizing capacity not less than 10 meq/dose to ensure sufficient efficacy within the physiological range. The improved method has been validated with respect to robustness to variations in sample preparation, repeatability and intermediate precision and has been cross-validated versus the RIGO method. The improved method has been found to be rather insensitive to variations in sample pretreatment and at least equivalent to the RIGO method.