The transformation process of transforming amorphous drug particles into crystalline particles was studied with itraconazole as the model drug, in which, three pharmaceutical acceptable surfactants were employed respectively as the additive, and micro-sized crystalline particles were successfully prepared. The effects of experimental parameters, such as crystallization time, temperature and the process of high-pressure homogenization (HPH), on the crystal form and particle size were investigated in detail. Experimental results show that the amorphous drug particles could be converted into crystalline particles in 10 min at room temperature by using poloxamer 407 (F127) as additive, and the particle size obtained could also be well controlled by the added F127. Under following HPH conditions: pressure of 100 Mpa and cycle times of 15, the particle size could be effectively reduced, and the crystalline itraconazole particles with an average size of 0.82 urn could be obtained. The micro-sized itraconazole powder was produced via spray drying method. Compared with the raw drug of itraconazole, the dissolution study indicates that the micro-sized itraconazole powder could effectively enhance the dissolution rate of the raw drug. It was found that, about 35.3% micro-sized drug could be dissolved within 20 min, whereas only 2.6% of the raw drug can be dissolved in the same period of time.%以水难溶性药物伊曲康唑为模型药物,研究了无定形纳米药物粒子的转晶过程,制备了超细伊曲康唑晶体颗粒,并研究了其溶出性能.实验采用三种药用表面活性剂作为添加剂,分别考察了它们对药物晶型的影响,并研究了转晶时间、温度以及高压均质过程对药物晶型及颗粒大小的影响.结果表明,以泊洛沙姆407(F127)为添加剂,可将无定形粒子转为结晶型颗粒,并可有效控制颗粒的粒径.适宜的转晶时间为10 min,实验可在室温下操作.高压均质过程可有效地减小晶体颗粒的大小,在均质压力100 MPa,均质次数为15次的条件下,可得到平均粒径为0.82 μm的超细晶体颗粒.通过喷雾干燥法,可得到超细伊曲康唑粉体.体外溶出度测试结果表明,超细伊曲康唑粉体的溶出速率远优于原料药,超细药物粉体20 min即可溶出35.3%,而同期原料药的溶出度只有2.6%.
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