Investigation of Polymer/Surfactant Interactions and Their Impact on Itraconazole Solubility and Precipitation Kinetics for Developing Spray-Dried Amorphous Solid Dispersions

摘要

Methods were developed to systematically screen different polymer–surfactant combinations for the purpose of enhancing amorphous active pharmaceutical ingredient (API) solubility while maintaining its physical stability. Itraconazole (ITZ) was chosen as the model API mostly due to its low aqueous solubility. Special attention was paid to determine the effect of a reduction in the critical micelle concentration (CMC) by specific polymer/surfactant combinations on the ITZ solubility and physical stability. However, only a slight correlation was actually found. Only the polymer/surfactant combinations with the smallest effect on CMC improved solubility and stability of ITZ in simulated intestinal fluids (SIF). Surfactants were found to negate the stabilizing effects of polymers. ITZ crystallization tendency generally depended on the degree of supersaturation and the type of polymer/surfactant combinations used. In general, we found that instead of focusing solely on reducing the CMC, a systematic screening of systems that maintain high ITZ supersaturation proved to be a successful approach.