In-Flow Flash Nanoprecipitation of Size-Controlled D-Leucine Nanoparticles for Spray-Drying Formulations

Abstract

We report the development of a novel flow-based method for the flash nanoprecipitation of size-controlled D-leucine nanoparticles for spray-drying formulations. Preliminary experiments were conducted in batch to define best flowable conditions that were then optimized considering nanoparticle size and distribution using a mesofluidic flow system. The method was applied to the streamilined preparation of D-leucine nanoparticles readily nebulized by mini and nano spray-dryer devices and characterized by SEM spectroscopy. Finally, the D-leucine atomized powder was used as glidant in dry powder for inhalation with micronized budesonide, a poorly water-soluble and low flowable anti-asthma drug.