Utilization of Diluted Compendial Media as Dissolution Test Solutions with Low Buffer Capacity for the Investigation of Dissolution Rate of Highly Soluble Immediate Release Drug Products.

Abstract

Research from the past decade has shown that the buffer capacities of intestinal fluids are much lower than those in the media used for dissolution test of many solid formulations. The purpose of this study was to elucidate the effect of buffer capacity on the dissolution profiles of highly soluble drug products, using metoclopramide (a biopharmaceutics classification system [BCS] class III drug) tablets as a model. The dissolution profiles of three metoclopramide products were obtained in Japanese pharmacopeia dissolution medium (pH 1.2 and 6.8), diluted medium with low buffer capacity comparable to that of gastrointestinal fluid, and other biorelevant media. One product showed slower dissolution in the medium with lower buffer capacity (bio-relevant, diluted compendial solution), but substantially similar dissolution in the compendial test solutions. Disintegration difference was implied to be involved in the different dissolution profiles depending on the medium buffer capacity. This study indicated the importance of media buffer capacity as a factor inducing different dissolution between products of highly soluble active pharmaceutical ingredients. The diluted compendial media would be a useful alternative to biorelevant media for the detection of the different formulation performances depending on the buffer capacities.