[Journal of Pharmaceutical Sciences] Novel budesonide particles for dry powder inhalation (DPI) prep
Budesonide is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers (MDI), nebulizers and dry powder inhalers (DPI). Inhalable drug particles are conventionally produced by crystallization followed by milling. This approach tends to generate partially amorphous materials that require post-processing to improve the formulations’ stability. Other methods involve homogenization or precipitation and often require the use of stabilizers, mostly surfactants. The purpose of this study was therefore to develop a novel method for preparation of fine budesonide particles using a microfluidic reactor coupled with ultrasonic spray freeze drying, and hence avoiding the need of additional homogenization or stabilizer use. A T-junction microfluidic reactor was employed to produce particle suspension (using an ethanol–water, methanol-water and an acetone–water system), which was directly fed into an ultrasonic atomization probe, followed by direct feeding to liquid nitrogen. Freeze drying was the final preparation step. The result were fine crystalline budesonide powders which, when blended with lactose and dispersed in an Aerolizer at 100 L/min, generated fine particle fraction in the range 47.6±2.8% to 54.9±1.8%, thus exhibiting a good aerosol performance. Subsequent sample analysis confirmed the suitability of the developed method to produce inhalable drug particles without additional homogenization or stabilizers. The developed method provides a viable solution for particle isolation in microfluidics in general.
Denis Saboti a, b, Uroš Maver c, Hak-Kim Chan a, Odon Planinšek b a Advanced Drug Delivery group, Faculty of Pharmacy, The University of Sydney, Building A15, NSW-2006, Australia b University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia c University of Maribor, Faculty of Medicine, Institute of Biomedical Sciences, Taborska ulica 8, SI-2000 Maribor, Slovenia