Antiprecipitant Screening System for Basic Model Compounds using Bio-Relevant Media

Abstract

Drug candidates with poor physicochemical properties (such as solubility) tend to have low bioavailability. For example, basic compounds might dissolve under acidic stomach conditions but then precipitate because of a change in pH under the neutral conditions found in the intestines. Therefore, it is essential to prevent precipitation and maintain high drug concentrations in the intestines to improve in vivo plasma exposure. Substances that act as antiprecipitants have been reported as well as bio-relevant media that mimic conditions in the stomach and small intestine. This report describes the development of an antiprecipitant screening system for basic model compounds using 96-well plates and bio-relevant media. Fourteen potential antiprecipitants were screened on one plate, which resulted in the identification of four substances that maintained a supersaturation state. To confirm these results, supersaturation studies were conducted according to the United States Pharmacopeia (USP) II dissolution method, and the results of the newly developed system correlated well with those of the USP II method. This novel system is useful for small-scale formulation screening during early preclinical development. This 96-well plate system will be available for the easily automated system in comparison with the conventional USP II system.