Influence of the Buffering Capacity of the Medium on the Dissolution of Drug-Excipient Mixtures

Abstract

The dissolution rates of benzoic acid/salicylic acid (BA/SA) and indomethacin/citric acid (IMC/CA) drug/excipient mixtures in media of different buffering properties were examined. The dissolution rates of the drug from both pure and mixed discs were found to be dependent on the buffering capacity of the dissolution medium. The acid excipient decreased the dissolution rate of the drug. In the presence of the second acid, the enhancing effect of increasing the buffer strength on the dissolution rate of the drug, was lowered. Buffer capacity versus pH profiles prepared for each buffer system showed the shape of these profiles to be an intrinsic property of the buffering agent(s) used. The differences in dissolution profiles observed in media of similar pH but different composition may be explained in terms of the buffering capacity of the medium. The pH-buffering capacity profiles of human duodenal aspirates were also examined. In contrast to the in vitro dissolution media, the human duodenal samples showed relatively constant buffering capacities in the pH range 4–8 and were below 20mm of HCl/litre. We conclude that the buffering capacity of the medium is an important consideration in the design of dissolution media if successful in vitro-in vivo correlation is to be obtained