School of Chemical and Biomolecular Engineering, University of Sydney, Australia.
Int J Pharm. 2010 Mar 30;388(1-2):114-22. doi: 10.1016/j.ijpharm.2009.12.047. Epub 2010 Jan 5.
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.
本研究旨在开发一种将无定形药物转化为结晶形式的方法，以提高其稳定性和吸入性能。采用超临界二氧化碳（scCO2）对喷雾干燥的无定形硫酸沙丁胺醇粉末进行处理，并用薄荷醇对其进行改性。考察了薄荷醇浓度、压力、温度和时间对所得硫酸沙丁胺醇粉末特性的影响。纯 scCO2 对无定形硫酸沙丁胺醇的物理性质没有影响；然而，在 150 巴和 50°C 下用薄荷醇改性的 scCO2 在 12 小时的处理后能够有效地将无定形药物转化为结晶形式。由于增加了表面粗糙度，颗粒之间的团聚减少，因此处理后粉末的平均粒径略有减小。用 scCO2+薄荷醇处理后，无定形硫酸沙丁胺醇的微细粒子分数（FPF（emitted））的发射剂量从 32%提高到 43%，其吸水率显著降低。本研究表明，scCO2+薄荷醇具有将粉末的无定形形式转化为结晶形式的潜力，同时保持了颗粒大小。
