黄芩苷脂质纳米泡沫气雾剂的制备工艺优化

Optimization of preparation technology of baicalin lipid nano foam aerosol

目的 优化黄芩苷脂质纳米泡沫气雾剂(BC-LN-FA)的制备工艺。方法 以黄芩苷(BC)为模型药物,采用薄膜分散法制备黄芩苷脂质纳米粒(BC-LN),采用均质乳化法制备BC-LN-FA;以粒径和包封率(EE)为指标,以投药量、乳化剂用量、助乳化剂用量、均质时间为考察因素,采用Box-Behnken设计-响应面法对其制备工艺进行优化,并对所得BC-LN-FA的形态、粒径、多分散系数(PDI)、EE、黏度、泡沫消解率和体外透皮释放等进行表征。结果 最优工艺为投药量25 mg、乳化剂(硬脂酸-大豆卵磷脂-甘油质量比1∶1∶1)用量40 mg、助乳化剂(十八醇-乳酸质量比1∶1)用量30 mg、均质时间20 min。3次验证实验结果显示,所制BC-LNFA的粒径为(151.70±2.40)nm、EE为(68.62±1.16)%(RSD均小于2%,n=3),与预测值(粒径150.80 nm、EE 67.02%)的偏差分别为0.60%、2.39%。按上述最优工艺所得BC-LN-FA乳液呈淡黄色,粒径均一且呈类圆形,黏度为(122.92±5.09)mPa·s,泡沫消解率为(65.32±3.22)%,BC含量为(7.01±0.12)%,PDI为(0.199±0.006);48 h时,其在pH7.4、6.8、5.0的磷酸盐缓冲液(PBS)中的累积释放百分率分别为(54.12±2.69)%、(57.85±4.25)%、(59.47±1.83)%,而游离BC在pH7.4的PBS中的累积释放百分率仅为(15.04±1.43)%。结论 所得最优工艺稳定、可行;所得BC-LN-FA粒度均匀,消泡快,具有一定黏度。

OBJECTIVE To optimize the preparation technology of the baicalin lipid nano foam aerosol(BC-LN-FA).METHODS Baicalin lipid nanoparticle(BC-LN)and BC-LN-FA were prepared by the thin film dispersion method and homogeneous emulsification method,respectively,using baicalin(BC)as the model drug. The preparation technology was optimized by BoxBehnken design-response surface methodology using particle size and encapsulation efficiency(EE) as indexes,with dosage,emulsifier dosage,co-emulsifier dosage and homogenization time as factors. The morphology,particle size,polymerdispersity index(PDI),EE,the viscosity,the foam dissolution rate and in vitro transdermal release of BC-LN-FA were characterized.RESULTS The optimal technology included 25 mg BC,40 mg emulsifier(mass ratio of stearic acid-soybean lecithin-glycerol was1∶1∶1),30 mg co-emulsifier(mass ratio of octadecanol-lactic acid was 1∶1),homogenization time of 20 min. Results of 3 times of validation tests showed that particle size of prepared BC-LN-FA was(151.70 ± 2.40) nm,EE was(68.62 ± 1.16)%;the deviation of them from the predicted value(particle size of 150.80 nm,EE of 67.02%)were 0.60% and 2.39% respectively. The BC-LN-FA prepared by the optimal process was light yellow opalescence,uniform in particle size and round-like in shape. The viscosity,the foam dissolution rate,the content of BC and PDI were(122.92±5.09)mPa·s,(65.32±3.22)%,(7.01±0.12)%and(0.199±0.006),respectively. At 48 h,the cumulative release rates of BC-LN-FA in phosphate buffer saline(PBS)at pH7.4,6.8,5.0 were(54.12±2.69)%,(57.85±4.25)% and(59.47±1.83)%,respectively;those of free BC in PBS at pH7.4 was only(15.04±1.43)%. CONCLUSIONS The optimized technology is stable and feasible. Prepared BC-LN-FA has a uniform particle size,high digestion rate and certain viscosity.