A novel method for the production of crystalline micronised particles.
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.
Muhammad
Syed Anuar Faua'ad Syed
SA
School of Chemical and Biomolecular Engineering, University of Sydney, Australia.
Langrish
Tim
T
Tang
Patricia
P
Adi
Handoko
H
Chan
Hak-Kim
HK
Kazarian
Sergei G
SG
Dehghani
Fariba
F
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
D000318:Adrenergic beta-Agonists; D014867:Water; D002245:Carbon Dioxide; D008610:Menthol; D000420:Albuterol