Barrett Angela Mary, Dehghani Fariba, Foster Neil R
School of Chemical Sciences and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia.
Pharm Res. 2008 Jun;25(6):1274-89. doi: 10.1007/s11095-007-9479-x.
The purpose of this study was to increase the dissolution rate of the poorly water soluble, antifungal drug Itraconazole.
Itraconazole was successfully micronized using both the gas antisolvent (GAS) and aerosol solvent extraction systems (ASES) using Acetone as the solvent. The affects of operating conditions such as temperature, pressure and solvent choice on variables such as morphology, particle size and dissolution were investigated. The influence of temperature in the range 25 to 40 degrees C and pressure between 90 and 190 bar were investigated.
Solvent choice was found to have the largest affect on particle production, with acetone found to be the optimal solvent choice when compared with dimethyl formamide (DMF), tetrahydrofuran (THF) and dichloromethane (DCM). Itraconazole particles with an average particle size of 6.9 microm were formed at the optimal ASES processing conditions of 40 degrees C and 190 bar. More significantly, in the first 100 minutes of dissolution 71.1% of the dense gas processed itraconazole was dissolved compared with 52.5% of Sporonox (the commercially available formulation) and 14.6% of the unprocessed material. Additional studies demonstrated that the formation of an itraconazole/PEG composite resulted in a 6-fold increase in dissolution rate in the first 100 min, to 89.8%, when compared to the unprocessed material.
Using ASES, microparticles of itraconazole were produced with an increased dissolution rate compared with raw material and commercially available product.
本研究的目的是提高水溶性差的抗真菌药物伊曲康唑的溶出速率。
以丙酮为溶剂，采用气体抗溶剂法（GAS）和气溶胶溶剂萃取系统（ASES）成功地将伊曲康唑微粉化。研究了温度、压力和溶剂选择等操作条件对形态、粒径和溶出度等变量的影响。研究了25至40摄氏度范围内的温度和90至190巴之间的压力的影响。
发现溶剂选择对颗粒生成的影响最大，与二甲基甲酰胺（DMF）、四氢呋喃（THF）和二氯甲烷（DCM）相比，丙酮是最佳的溶剂选择。在40摄氏度和190巴的最佳ASES加工条件下，形成了平均粒径为6.9微米的伊曲康唑颗粒。更显著的是，在溶出的前100分钟内，71.1%的经致密气体处理的伊曲康唑溶解，相比之下，斯皮仁诺（市售制剂）为52.5%，未加工材料为14.6%。进一步的研究表明，与未加工材料相比，伊曲康唑/聚乙二醇复合材料的形成使前100分钟的溶出速率提高了6倍，达到89.8%。
使用ASES制备的伊曲康唑微粒，其溶出速率比原料和市售产品有所提高。
