Establishment of Fundamental Production Technique for Inhaled High-Dose Dry Powders

Abstract

In the present study, we attempted to produce inhaled high-dose dry powder formulations for an active pharmaceutical ingredient (API) with poor aqueous solubility using several additives by spray freeze drying (SFD) and spray drying (SD) techniques. Scanning electron microscopy revealed that the SFD powders composed of 50% API were highly porous and spherical microparticles with diameters of 5–15 μm, the SFD powders composed of 90% API were aggregates constructed with submicron-sized primary particles, and the SD powders composed of 50% API were corrugated microparticles with diameters of 0.5–5 μm. Toxicity assessment using an air–liquid interface-cultured cell layer confirmed the relatively high safety of the additives used. Particle size distribution measurements clarified that both the SFD and SD powders could be efficiently dispersed in air using an inhalation device, whereas the SFD powders had higher air dispersibility than the SD powders. Aerosol performance evaluation demonstrated that the SFD powders composed of 90% API achieved the fine particle fraction (FPF) of approximately 50%, enabling the maximum possible amount of API to be delivered to the lungs through inhalation.