前列地尔微乳的冻干工艺的筛选及制备工艺的优化

Screening of Freeze-drying Parameters and Formulation Optimization of Alprostadil-loaded Microemulsions

前期研究表明,前列地尔微乳冻干后再复溶的包封率显著下降。为此,考察了冻干工艺的温度设置和升温速率对包封率的影响。结果显示,冻干工艺中所设定的升温速度对包封率无明显影响。根据体系含水量和电导率值关系的曲线,确定了o/w型微乳形成的临界点。通过绘制伪三元相图并以粒径和包封率为考察指标,筛选处方中乳化剂和助乳化剂质量比(K_m)、油相组成和药脂比等。确定优化处方中各参数值分别为:混合乳化剂(MSA)中K_m值为6∶1;油相组成为MCT∶大豆油(1∶3);药脂比为1∶3 000;MSA∶油相质量比为8∶2。3批优化微乳的冻干品复溶后平均粒径约为82.6 nm,包封率约为85%。

Our previous study showed that entrapment efficiency of the lyophilized alprostadil-loaded microemulsions significantly decreased after reconstitution. So, the influences of temperature program and elevating rate of shelf temperature on entrapment efficiency of the microemulsions were investigated. The results showed that freeze- drying parameters had no significant influences on entrapment efficiency. Accordint to the conductivity-water content curve, the critical water content of O/W microemulsions formation was ascertained. The pseudo-ternary phase diagrams were drawn to optimize the parameters of formulation with droplet diameter and entrapment efficiency as indexes. The optimal formulation parameters were as follows： the value of Km 6 ： 1; weight ratio of medium chain triglyceride （MCT） to soybean oil 1 ： 3; drug-to-lipid ratio 1 ： 3 000; weight ratio of the mixed surfactant （MSA） to oil phase 8 ： 2. The mean droplet diameter and entrapment efficiency of three batches of the lyophilized optimal microemulsions after reconstitution were about 82.6 nm and 85 %, respectively.