title: Novel Budesonide Particles for Dry Powder Inhalation Prepared Using a Microfluidic Reactor Coupled With Ultrasonic Spray Freeze Drying.
abstract: Budesonide (BDS) is a potent active pharmaceutical ingredient, often administered using respiratory devices such as metered dose inhalers, nebulizers, and dry powder inhalers. 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 BDS 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 was fine crystalline BDS 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.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Building A15, NSW-2006, Australia; University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, Ljubljana 1000, Slovenia.
authors.forename: Denis
authors.initials: D
authors.lastname: Saboti
authors.affiliation: University of Maribor, Faculty of Medicine, Institute of Biomedical Sciences, Taborska ulica 8, Maribor SI-2000, Slovenia.
authors.forename: Uroš
authors.initials: U
authors.lastname: Maver
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Building A15, NSW-2006, Australia. Electronic address: kim.chan@sydney.edu.au.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, Ljubljana 1000, Slovenia. Electronic address: odon.planinsek@ffa.uni-lj.si.
authors.forename: Odon
authors.initials: O
authors.lastname: Planinšek
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D019819:Budesonide / Q000008:administration & dosage* / Q000737:chemistry; D003460:Crystallization; D004339:Drug Compounding / Q000295:instrumentation*; D058995:Dry Powder Inhalers; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying / Q000295:instrumentation*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D007785:Lactose / Q000737:chemistry; D010316:Particle Size; D011208:Powders; D014465:Ultrasonics / Q000295:instrumentation*
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D005079:Excipients; D011208:Powders; D019819:Budesonide; D007785:Lactose
keywords: DPI; aerosol; budesonide; dry powder inhalation; formulation; microfluidic reactor; particle isolation; powder technology; pulmonary drug delivery; ultrasonic spray freeze drying