Uniform Spray Dried Loxapine Microparticles Potentially for Nasal Delivery: Exploring Discriminatory In Vitro Release Evaluation Methods.

Abstract

This study aimed to develop suitable in vitro evaluation methods for the release behavior of nasal powders (NPs). We synthesized a range of standardized microparticles with adjustable size and morphology by co-spray-drying loxapine succinate (LOX) and gelatin (GEL) using an ethanol/water solvent mixture in a self-designed micro-fluidic jet spray dryer (MFJSD). The influence of the LOX/GEL mass ratio and solvent composition on particle characteristics, including size, morphology, and crystalline properties, was systematically investigated. In vitro release profiles of NPs were thoroughly assessed across different release medium, apparatus, and membranes. The modified Transwell^® system, utilizing simulated nasal electrolyte solution (SNES) as the release medium, was identified as the most effective in distinguishing the performance of microparticles with diverse attributes. Furthermore, the impact of particle size, morphology, and crystalline properties on in vitro release profiles was discussed. This research presents a robust methodology for the in vitro evaluation of NPs release profiles and provides a practical approach for the rational fabrication of high-quality NPs products.