A novel method for the production of crystalline micronised particles

作者：Muhammad Syed Anuar Faua'ad Syed; Langrish Tim; Tang Patricia; Adi Handoko; Chan Hak Kim; Kazarian Sergei G; Dehghani Fariba^*

来源：International Journal of Pharmaceutics, 2010, 388(1-2): 114-122.

DOI：10.1016/j.ijpharm.2009.12.047

• Supercritical CO(2)
• Salbutamol sulphate
• Menthol
• Crystallisation
• Inhalation drug delivery

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 150 bar and 50 degrees C was efficient in converting amorphous drug to crystalline form after 12 h of conditioning. The average particle size of powders decreased slightly after the conditioning process because of reducing agglomeration between particles by increasing surface toughness. 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.

• 出版日期2010-3-30