Beatriz Behrend-Keim1, Miguel O. Jara1,2, Daniel A. Davis Jr. 3, Dave A. Miller3, Robert O. Williams III¹.
1Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, Austin, TX, 78712, USA
2Present address: Departamento de Ciencias y Tecnología Farmacéuticas, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380492, Chile
3AustinPx, 111 W. Cooperative Way, Georgetown, TX 78626, USA
Summary
This study introduces powder discharge-based KinetiSol (pKSD) as a novel particle engineering process for manufacturing dry powders suitable for inhalation. pKSD is a KinetiSol-derived method that, through modified parameters, produces powder blends rather than conventional melt agglomerates. Kinetisol technology is a scalable, solvent-free process that is primarily used to produce amorphous solid dispersions. Now, we have adapted KinetiSol, identifying pKSD as a high-energy mixing technique capable of generating nano- and micron-sized particulate aggregates with a higher bulk density, enabling high-dose drug loading. The research focuses on pKSD’s potential for improving the solubility of poorly water-soluble drugs; however, a deeper understanding of its influence on excipient morphology and subsequent aerosol performance is required to apply it to pulmonary drug delivery.
In this study, we investigated pKSD’s capability to produce powder blends for inhalation using crystalline L-leucine and amorphous cyclodextrins. We evaluated their aerosol performance, bulk densities, and the impact of the pKSD process on particle size and morphology. Results showed that pKSD significantly reduced the particle size of L-Leucine and hydroxypropyl-β-cyclodextrin (HPBCD), leading to an approximately 50% fine particle fraction (FPF), which is comparable to that of commercially approved products. Conversely, sulfobutyl ether-β-cyclodextrin (SBECD) retained its original morphology and size, resulting in a lower FPF (21%). In conclusion, pKSD effectively modifies powder blend characteristics based on excipient properties. Additionally, the higher bulk densities achieved with pKSD, compared to spray-dried formulations, make pKSD a suitable particle engineering approach for targeted high-dose drug delivery to the lungs.