In Vitro Dissolution Tests Corresponding to the in Vivo Dissolution of Clarithromycin Tablets in the Stomach and Intestine

Abstract

The correlation between in vivo and in vitro dissolution of clarithromycin (CAM) tablets was examined. In vivo dissolution rate constants in the stomach and the intestine were obtained from analysis of the urinary excretion data of CAM following oral administration to humans in the fasting or postprandial state using a pharmacokinetic model including gastrointestinal transit. In the present study, the flow-through cell method with moderate agitation was used, as the in vitro dissolution test related to the in vivo dissolution rate constants. Both the effects of pH of the dissolution medium and the volumetric solvent flow rate on the dissolution rate in the flow-through cell method were examined. The pH of the dissolution medium and the flow rate were related to the in vitro dissolution rate. Therefore, the conditions of the flow-through cell method in correlation with the in vivo dissolution rates in the stomach and intestine were determined by controlling the flow rate at pH 3.0 and 6.8 dissolution medium. The urinary excretion of CAM, simulated by substituting the in vitro dissolution rate constants into the equation, were consistent with the in vivo data. The in vitro tests corresponding to the in vivo dissolution in the stomach and intestine following a single oral administration in the fasting or postprandial state for a CAM tablet were established. © 1995, The Pharmaceutical Society of Japan. All rights reserved.