Z-综合评分法优化丹皮酚阳离子脂质体凝胶剂制备工艺

Optimization of Preparation Technology for Paeonol Cation Liposome Gel by Z-comprehensive Score Method

目的:优化丹皮酚阳离子脂质体凝胶剂的制备工艺。方法:采用薄膜分散-探头超声法结合研磨法制备丹皮酚阳离子脂质体凝胶,以包封率、粒径大小及ξ电位为考察指标,以中性脂材/带电脂材摩尔比、药脂比、水化时间和超声条件因素,每因素采取3个水平,利用正交试验优化制备工艺。结果:最佳制备工艺为DC-Chol 160 mg,Chol 300 mg,HSPC 500 mg,溶于40 mg丹皮酚三氯甲烷液(15 mL)中,40℃水浴减压蒸发除去有机溶剂,形成均匀薄膜,加入pH 6.5磷酸盐缓冲液(PBS,0.05 mol.L-1)10 mL水化2 h,探头式超声3 min,再依次过0.8,0.45μm的微孔滤膜,得脂质体溶液。另取卡波姆1.0 g,加入脂质体溶液中,溶胀完全后,加入甘油0.3 g,研磨均匀,即得。结论:薄膜分散-探头超声法结合研磨法制备脂质体凝胶,脂质体包封率较高、粒径分布均匀、ξ电位适宜,制剂黏度佳,刺激性小。

Objective：To investigate optimization of preparation technology for paeonol cation liposome gel.Method：Paeonol cation liposome gel was prepared by dispersion-ultrasonic combined with grinding method,with encapsulation efficiency,particle size and ξ potential as indexes,L9（34）orthogonal design was used to optimize preparation technology,factors were chosen as amount of substance ratio of DC-Chol /Chol,lipid/drugs,hydration time and ultrasonic condition.Result：Optimum preparation technology was as follows：weigh of DC-Chol was 160 mg,Chol 300 mg and HSPC 500 mg,added into 40 mg paeonol solution dissolved by 15 mL chloroform,evaporated and removed organic solvent to form uniform film at 40 ℃,added 10 mL pH 6.5 phosphate buffer solution to hydrate for 2 h,probe ultrasound for 3min,and then filter by 0.8,0.45 μm microporous membrane,liposome solution was obtained.Meanwhile,took carbomer 1.0 g,added into liposome solution,swelled completely,dropped into 0.3 g glycerin,ground to form uniform gel preparations.Conclusion：Using film dispersion-ultrasonic and gridding method,we prepared cation liposomes gel containing paeonol with liposome having high entrapment efficiency,uniform size distribution and moderate ξ potential,gel preparation had moderate viscosity and slight irritation.