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.

中文翻译：

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评估血管内给药产品性能的体外条件：使用两性霉素B作为模型药物，开发适当的测试介质。

目前，没有专门针对肠胃外制剂的药典体外释放试验。考虑生物相关和临床相关的测试介质代表了开发体外测试的一种有价值的方法，该方法理想地可以提供有关体内制剂性能的信息。这项研究的目的是研究不同培养基成分对两性霉素B（一种难溶性高蛋白结合药物）的溶解度的影响，以便开发生物相关的和临床相关的培养基，以便将来从其脂质体制剂中进行体外释放测试。在开发方法中考虑了三类介质：第一类介质：白蛋白浓度的影响；第二类介质：白蛋白浓度的影响。第2类介质：血浆成分（胆汁盐，磷脂，胆固醇，白蛋白）; 第3类介质：在有或没有白蛋白的情况下，使用与生物有关的和合成的表面活性剂达到临床相关的溶解度，并为开发模拟的低白蛋白血症血浆介质奠定了基础。所有测试的表面活性剂均增加了两性霉素B的溶解度，而同时存在的白蛋白则对溶解度产生负面影响。开发了使用生物相关或合成表面活性剂和白蛋白的临床相关介质。一种减少两性霉素B溶解度的培养基被确定为模拟低白蛋白血症血浆的潜在候选培养基。生物相关和临床相关介质的开发以及对介质成分及其相互作用的影响的理解，