Experimental investigations of particle formation from propellant and solvent droplets using a monodisperse spray dryer

Abstract

Experimental studies of particle formation from solution droplets were conducted using a newly developed monodisperse spray drying process. Solutes beclomethasone dipropionate and caffeine were dissolved in ethanol, pressurized hydrofluoroalkane propellant 134a, and mixtures thereof. Solutions were atomized into monodisperse microdroplets using a custom droplet generator installed in a laboratory scale spray dryer, enabling drying and collection of the resulting monodisperse microparticles. The effects of droplet diameter, solution concentration, solvent composition, and drying rate on the physical properties of the dried particles were evaluated. Particle morphology and size were assessed using ultramicroscopy and image analysis of micrographs. Extent of crystallinity and polymorphism were investigated using Raman spectroscopy. The drying temperature was found to have a large effect on the morphology of amorphous beclomethasone dipropionate particles. Particles dried near room temperature were spheroidal to ellipsoidal with prevalent surface concavities and evidence of shell buckling; increasing the drying temperature for fixed droplet size and composition resulted in a transition to more spherical, smooth-surfaced particle morphologies. Crystalline caffeine microparticles were made up of assemblies of multiple crystallites. The measured length and breadth of these crystallites was found to be correlated with the time available for crystal nucleation and growth as calculated using a particle formation model. The results highlight the abilities and limitations of currently available particle formation models in elucidating the relationships between the size, composition, and evaporation rate of drying solution droplets and the physical properties of the resulting particles. The work demonstrates the suitability of monodisperse spray drying as an experimental technique for investigating the fundamentals of particle formation from solution droplets.© 2018 American Association for Aerosol Research