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

06 May 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


In this work we report the development of a cheap and scalable flow-based flash nanoprecipitation approach to prepare D-leucine nanoparticles particularly useful as glidants in dry powder for inhalation. Starting from preliminary batch screens, the process was successfully optimized and scaled-up under mesofluidic conditions. The nebulization with both mini and nano spray-dryer, the SEM analysis of nanoparticles and the aerodynamic evaluation of a formulation obtained by physical mixing of atomized D-leucine powders with budenoside showed an excellent decrease in particle size without altering the morphology, and a marked improvement in the aerodynamic properties of the drug. This simple and economic method by physical mixing of leucine with micronized active pharmaceutical ingredients can represent a valid alternative to co-spray-drying.


nanoprecipitation method
flow reactors
Spray Drying

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