In vitro conditions for performance evaluation of products for intravascular administration: Developing appropriate test media using Amphotericin B as a model drug

Currently, there are no compendial in vitro release tests specifically indicated for parenteral formulations. Consideration of biorelevant and clinically relevant test media represents a valuable approach for the development of in vitro tests that ideally can provide information on the formulation performance in vivo. The aim of this study was to investigate the effect of different media components on the solubility of Amphotericin B (a poorly soluble highly protein-bound drug) in order to develop biorelevant and clinically relevant media for future in vitro release testing from its liposomal formulation. Three categories of media were considered in the development approach: Category 1 media: effect of albumin concentration; category 2 media: effect of biorelevant concentrations of plasma components (bile salts, phospholipids, cholesterol, albumin); category 3 media: attaining clinically relevant solubility with biorelevant and synthetic surfactants with and without albumin and setting the basis for the development of a simulated hypoalbuminaemic plasma medium. All the surfactants tested increased Amphotericin B solubility while the simultaneous presence of albumin had a negative effect on solubility. Clinically relevant media with the use of biorelevant or synthetic surfactants and albumin were developed. One medium in which the solubility of Amphotericin B was reduced was identified as potential candidate medium to simulate hypoalbuminaemic plasma. The development of biorelevant and clinically relevant media and understanding the effect of media components and their interactions, supports future development of meaningful in vivo predictive release tests for parenteral formulations.