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Download fileIntegrated Continuous Plug-Flow Crystallization and Spray Drying of Pharmaceuticals for Dry Powder Inhalation
journal contribution
posted on 2019-08-20, 18:35 authored by Gabriela
Daisy Hadiwinoto, Philip C. L. Kwok, Henry H. Y. Tong, Si Nga Wong, Shing Fung Chow, Richard LakerveldThe
manufacture of dry powders for pulmonary drug delivery is complicated
by stringent requirements for the aerodynamic size distribution and
solid-state properties of the powder. Micronization is often needed
after conventional batch crystallization to reduce the particle size,
which lowers the process yield and may lead to particles with poor
aerosolization behavior. A novel process combining continuous plug-flow
crystallization and spray drying is presented to produce crystals
with optimal properties for pulmonary drug delivery in a single step.
Continuous flow enables fast nucleation with antisolvent crystallization.
Subsequently, the narrow and controllable residence time distribution
of segmented-flow crystallization is exploited to grow the crystals
uniformly into the optimal size range for pulmonary drug delivery.
Finally, the solvent is evaporated rapidly using spray drying in a
continuous flow. Two case studies involving relevant drugs for pulmonary
delivery are presented to demonstrate practical relevance and process
flexibility. The process can be optimized for both cases such that
a dry powder with excellent aerosolization behavior is produced. The
novel process is simple and flexible due to the clear separation of
process functions and the availability of sufficient process variables
for optimization.