摘要
目的研究地西泮的纳米结构脂质载体(nanostructured lipid carrier,NLC)的处方用量与制备工艺的优化,确定最佳的处方用量与制备工艺。方法采用高压均质法制备地西泮的纳米结构脂质载体,以纳米粒粒径与包封率为考察指标,运用单因素设计的方法对固液态油脂比、脂质用量、乳化剂用量、药脂比、均质压力与均质次数进行了考察,并采用L_9(3~4)正交表设计正交实验优化制备工艺;以处方用量与制备工艺验证、稳定性及体外释放实验对地西泮的NLC制剂学进行了考察。结果确定最佳处方用量及制备工艺为GSM与油酸投料比为10∶3,药脂比为1∶50,TPGS用量为1.4 g,乳化剂用量1.2 g,高压均质压力为70 m Pa,均质次数3次。依据最佳处方量和制备工艺得出地西泮NLC的平均包封率为(81.94±0.98)%及粒径为(133.2±2.3)nm。结论单因素试验联合正交试验可有效地优化地西泮NLC的处方用量与制备工艺,优化条件下制备的地西泮NLC具有较高的包封率,粒径较小且分布均匀,24 h内稳定性良好,且体外释放率曲线符合Higuchi模型。
Objective To study the best dosage and preparation process optimization of nanostructured lipid carrier （ NLC ） for diazepam. Methods The nanostructured lipid carrier for diazepam was prepared by high pressure homogenization method. The nanoparticle size and entrapment efficiency were used as indicators. The single-factor design method was used to investigate the ratio of solid-liquid lipid, lipid, emulsifier, drug-lipid ratio, homogenization pressure and homogenization times ; and the orthogonal design of L9 （34 ） orthogonal table design was used to optimize the preparation process. The NLC preparation for diazepam was tested with the prescription dosage, preparation process, stability and in vitro release. Results The best formula dosage and preparation process were determined as follows ： the ratio of GSM to oleic acid was 10 ： 3, the ratio of lipid to lipid was 1 ： 50, the amount of TPGS was 1.4 g, the amount of emulsifier was 1.2 g, the homogenization pressure was 70 mPa, the times of homogenization was 3. The average entrap- ment efficiency of diazepam NLC was （81.94± 0. 98）% and the particle size was （ 133.2 ± 2. 3） nm according to the best formula dosage and preparation process. Conclusion The single factor test can effectively optimize the dosage and preparation process of NLC for diazepam together with the orthogonal test. The NLC for diazepam prepared under optimized conditions is small and uniform and of high encapsulation efficiency. The internal stability is in good agreement with the Higuchi model.
出处
《锦州医科大学学报》
CAS
2017年第1期6-11,I0002,I0003,共8页
Journal of Jinzhou Medical University
关键词
地西泮
纳米结构脂质载体
制剂学
diazepam
nanostructured lipid carrier
manufacturing pharmacy
