A novel method for the production of crystalline micronised particles

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• 作者：Syed Anuar Faua’ ; ad Syed Muhammad ; Tim Langrish ; Patricia Tang ; H ; oko Adi ; Hak-Kim Chan ; Sergei G. Kazarian ; Fariba Dehghani
• 关键词：Supercritical CO₂ ; Salbutamol sulphate ; Menthol ; Crystallisation ; Inhalation drug delivery
• 刊名：International Journal of Pharmaceutics
• 出版年：2010
• 出版时间：30 March 2010
• 年：2010
• 卷：388
• 期：1-2
• 页码：114-122
• 全文大小：903 K

文摘

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 (scCO₂) modified with menthol. The effect of menthol concentration, pressure, temperature and time on the characteristics of the resulting salbutamol sulphate powder was investigated. Pure scCO₂ had no effect on the physical properties of amorphous salbutamol sulphate; however, scCO₂ modified with menthol at 150 bar and 50 °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 roughness. Emitted dose measured by the fine particle fraction (FPF_emitted) of amorphous salbutamol sulphate was enhanced from 32 % to 43 % after conditioning with scCO₂ + menthol and its water uptake was significantly decreased. This study demonstrates the potential of scCO₂ + menthol for converting amorphous forms of powders to crystalline, while preserving the particle size.