title: A novel method for the production of crystalline micronised particles.
abstract: The aim of this study was to develop a method for converting an amorphous drug to a crystalline form to enhance its stability and inhalation performance. Spray-dried amorphous salbutamol sulphate powder was conditioned with supercritical carbon dioxide (scCO(2)) modified with menthol. The effect of menthol concentration, pressure, temperature and time on the characteristics of the resulting salbutamol sulphate powder was investigated. Pure scCO(2) had no effect on the physical properties of amorphous salbutamol sulphate; however, scCO(2) modified with menthol at 150bar and 50 degrees C was efficient in converting amorphous drug to crystalline form after 12h of conditioning. The average particle size of powders decreased slightly after the conditioning process because of reducing agglomeration between particles by increasing surface roughness. Emitted dose measured by the fine particle fraction (FPF(emitted)) of amorphous salbutamol sulphate was enhanced from 32% to 43% after conditioning with scCO(2)+menthol and its water uptake was significantly decreased. This study demonstrates the potential of scCO(2)+menthol for converting amorphous forms of powders to crystalline, while preserving the particle size.
authors.affiliation: School of Chemical and Biomolecular Engineering, University of Sydney, Australia.
authors.forename: Syed Anuar Faua'ad Syed
authors.initials: SA
authors.lastname: Muhammad
authors.forename: Tim
authors.initials: T
authors.lastname: Langrish
authors.forename: Patricia
authors.initials: P
authors.lastname: Tang
authors.forename: Handoko
authors.initials: H
authors.lastname: Adi
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.forename: Sergei G
authors.initials: SG
authors.lastname: Kazarian
authors.forename: Fariba
authors.initials: F
authors.lastname: Dehghani
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry*; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D016503:Drug Delivery Systems; D004355:Drug Stability; D008610:Menthol / Q000737:chemistry; D010316:Particle Size; D013499:Surface Properties; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000318:Adrenergic beta-Agonists; D014867:Water; D002245:Carbon Dioxide; D008610:Menthol; D000420:Albuterol