Flow nanoprecipitation of size-controlled d-leucine nanoparticles for spray-drying formulations

Abstract

The increasing interest in the use of nanoparticles for biomedical applications has resulted in a growing demand for efficient and scalable methods that enable their preparation with fine control over particle size, distribution and morphology. In this work we report 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 the best flowable conditions that were then optimized considering the nanoparticle size and distribution using a mesofluidic flow system. The method was applied to the streamlined preparation of D-leucine nanoparticles readily nebulized using mini and nanospray-dryer devices and characterized by SEM analysis. Finally, the D-leucine atomized powder was used as a glidant in dry powder for inhalation with micronized budesonide, a poorly water-soluble and low flowable anti-asthma drug.