Update on Gastrointestinal Biorelevant Media and Physiologically Relevant Dissolution Conditions

摘要

Dissolution testing constitutes one of the most widely used in vitro performance tests during drug development and routine quality control testing. It monitors the rate and extent of in vitro drug release (batch release test), and it is often used to ensure consistent in vivo performance. The purpose of this review is to summarize and update the many physiologically adapted media and buffers proposed over the years, focusing on the upper gastrointestinal tract because this is where most drug absorption occurs. Emphasis will be given on the application of bicarbonate-based media because this is the major buffering species in the human intestinal lumen. Due to the pragmatical difficulties of using bicarbonate-based dissolution media, surrogate media with simpler buffer systems are desirable. Herein we describe some of the proposed models and different approaches to develop such substitutes. Special consideration has to be taken when dealing with enteric coated (delayed release) formulations because the interaction of coating polymer with bicarbonate is very complex. All factors considered, using physiologically relevant conditions can ameliorate the risks and enable drug development with increased likelihood to select formulations with the desired in vivo performance.