Aerosol Synthesis of Inhalation Particles via a Droplet-to-Particle Method

ABSTRACT

Inhalation powders with consistent particle properties, including particle size, size distribution, and shape were produced with an aerosol synthesis method. Compared to conventional spray drying, the aerosol method provides better control of the thermal history and residence time of each droplet and product particle due to the laminar flow in the heated zone of the reactor where the droplet drying and particle formation take place. A corticosteroid, beclomethasone dipropionate, generally used for asthma treatment was chosen as a representative material to demonstrate the process. Spherical particles were produced with a droplet-to-particle method from an ethanolic precursor solution. The droplets produced with an ultrasonic nebulizer were carried to a heated zone of the reactor at 50–150°C where the solvent was evaporated and dry particles formed. The mass mean diameter of the particles were well within the respirable size range (approximately 2 μm). The geometric standard deviation (GSD) of produced particles was approximately 2. The particle surface structure varied from smooth to rough depending on the degree of particle crystallinity and was affected by the thermal history of the particle. Amorphous particles with smooth surface were most likely obtained due to the rapid evaporation of the solvent from the droplet combined with the slow diffusion of the beclomethasone dipropionate molecule. The amorphous particles were transformed slowly to crystalline particles in the open atmosphere. In addition, the particle surface structure changed from smooth to rough during storage. The process was accelerated by thermal post-annealing. However, additional heating also increased particle sintering. By optimizing the reactor parameters, and thus increasing the molecular diffusion, stable, crystalline particles were produced at 150°C.

Keywords:

• inhalation particle
• formation
• crystallization
• aerosol method