title: Influence of primary crystallisation conditions on the mechanical and interfacial properties of micronised budesonide for dry powder inhalation.
abstract: Investigate the influence of primary crystallisation conditions on the mechanical properties and secondary processing behaviour of budesonide for dry powder inhaler (DPI) formulations. Young's modulus of two batches of budesonide crystals (samples A and B) produced using different anti-solvents was determined using nanoindentation. Physicochemical and surface interfacial properties via the cohesive-adhesive balance (CAB) approach to colloid probe atomic force microscopy (AFM) of air-jet micronised budesonide crystals were also investigated. These data were correlated to in vitro aerosolization performance of carrier-based DPI formulations containing either budesonide samples A or B and lactose monohydrate. Young's modulus of budesonide samples A and B crystals was 0.95 and 4.04 GPa, respectively. Sample A crystals with low Young's modulus exhibited poorer micronisation efficiency than sample B. CAB analysis of micronised budesonide samples A and B, suggest that sample B budesonide had a greater adhesion to lactose than sample A. These data correlated with in vitro aerosolisation studies, which showed that the fine particle delivery of budesonide sample A was higher than that of sample B. In conclusion, crystallisation conditions may affect the mechanical properties of budesonide, and therefore secondary processing of the material and their interfacial properties and product performance in carrier based DPI formulations.
authors.affiliation: Pharmaceutical Surface Science Research Group, Department of Pharmacy and Pharmacology, University of Bath, BA2 7AY, UK.
authors.forename: Harshal A
authors.initials: HA
authors.lastname: Kubavat
authors.forename: Jagdeep
authors.initials: J
authors.lastname: Shur
authors.forename: Graham
authors.initials: G
authors.lastname: Ruecroft
authors.forename: David
authors.initials: D
authors.lastname: Hipkiss
authors.forename: Robert
authors.initials: R
authors.lastname: Price
mesh_terms: D000096:Acetone / Q000737:chemistry; D000280:Administration, Inhalation; D000336:Aerosols; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003102:Colloids; D003460:Crystallization; D004126:Dimethylformamide / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D058995:Dry Powder Inhalers; D055119:Elastic Modulus; D007785:Lactose / Q000737:chemistry; D018625:Microscopy, Atomic Force; D036103:Nanotechnology; D010316:Particle Size; D011208:Powders; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D003102:Colloids; D004337:Drug Carriers; D011208:Powders; D012997:Solvents; D014867:Water; D000096:Acetone; D019819:Budesonide; D004126:Dimethylformamide; D007785:Lactose