乙醇注入法制备高乌甲素脂质体凝胶的工艺研究
|
摘要
目的:优化高乌甲素脂质体制备处方及工艺,考察其经皮吸收能力。方法:采用乙醇注入法制备高乌甲素脂质体,并用正交试验法确定高乌甲素脂质体的优选工艺;建立高乌甲素高效液相含量测定方法,以包封率及粒径评价脂质体质量;进一步制备高乌甲素脂质体凝胶,并采用透皮吸收试验评估透皮吸收能力。结果:正交试验确定高乌甲素脂质体最佳处方工艺组合为卵磷脂:胆固醇为6∶1、药脂比为1∶30、水化温度为55℃。按最佳处方得到的脂质体结构完整,平均包封率为(61. 32±2. 82)%,平均粒径为(314. 7±0. 45) nm,平均Zeta电位为(-28. 6±0. 21) m V。透析袋释放试验与体外透皮试验显示,与普通高乌甲素凝胶相比,脂质体透皮速率缓慢,具有缓释作用。结论:乙醇注入法制备高乌甲素脂质体工艺简单可行,可得到包封率高、粒径较小的高乌甲素脂质体,并且能使药物在皮肤蓄积,达到缓释的效果。
Objective: To optimize the formulation and preparation of lappaconitine liposomes and investigate the transdermal absorbability. Methods: An ethanol injection method was used to prepare lappaconitine liposomes,and the orthogonal method was used to determine the optimal preparation process of appaconitine liposomes. An HPLC method was established to determine the drug content,the liposomes quality was evaluated with the encapsulation efficiency and particle size as the indices. Lappaconitine liposomal gel was further prepared and the transdermal absorbability was evaluated by transdermal absorption assay. Results: The best formulation of lappaconitine liposomes optimized by orthogonal test was as follows: the ratio of lecithin to cholesterol was 6∶ 1,the ratio of drug to lipids was 1∶ 30,and the hydration temperature was 55℃. The liposomes prepared according to the best formulation were with complete structure,the encapsulation efficiency of(61. 32 ± 2. 82) %,the average particle diameter of(314. 7 ± 0. 45) nm,and the zeta potential of(-28. 6 ± 0. 21) m V. The in vitro transdermal experiments showed the liposomal gel had slower skin penetration rate and drug release when compared with the common lappaconitine gel. Conclusion: The ethanol injection method is simple and feasible for the preparation of lappaconitine liposomes with high encapsulation efficiency and small particle size,and the drug can be accumulated in the skin to achieve sustained release.
Objective: To optimize the formulation and preparation of lappaconitine liposomes and investigate the transdermal absorbability. Methods: An ethanol injection method was used to prepare lappaconitine liposomes,and the orthogonal method was used to determine the optimal preparation process of appaconitine liposomes. An HPLC method was established to determine the drug content,the liposomes quality was evaluated with the encapsulation efficiency and particle size as the indices. Lappaconitine liposomal gel was further prepared and the transdermal absorbability was evaluated by transdermal absorption assay. Results: The best formulation of lappaconitine liposomes optimized by orthogonal test was as follows: the ratio of lecithin to cholesterol was 6∶ 1,the ratio of drug to lipids was 1∶ 30,and the hydration temperature was 55℃. The liposomes prepared according to the best formulation were with complete structure,the encapsulation efficiency of(61. 32 ± 2. 82) %,the average particle diameter of(314. 7 ± 0. 45) nm,and the zeta potential of(-28. 6 ± 0. 21) m V. The in vitro transdermal experiments showed the liposomal gel had slower skin penetration rate and drug release when compared with the common lappaconitine gel. Conclusion: The ethanol injection method is simple and feasible for the preparation of lappaconitine liposomes with high encapsulation efficiency and small particle size,and the drug can be accumulated in the skin to achieve sustained release.
引文
1徐斌,张琴,郭夫江,等.高乌头研究进展[J].中成药,2016,38(4):882-890
2李思思,张洪兵,朱雪瑜.高乌甲素新型制剂的研究进展[J].现代药物与临床,2014,29(7):818-823
3侯丽芬,谷克仁,吴永辉.不同制剂脂质体制备方法的研究进展[J].河南工业大学学报,2016,37(5):118-124
4 Lin L,Zhu Y,Thangaraj B,et al.Improving the stability of thyme essential oil solid liposome by usingβ-cyclodextrin as a cryoprotectant[J].Carbohydrate Polymers,2018,188:243-251
5付金芳,曹伶俐,李乘欣,等.氢溴酸高乌甲素纳米粒缓释片的制备[J].中成药,2017,39(5):952-955
6张晓丽,吴品昌,刘宇,等.乙醇注入法制备莪术醇脂质体[J].中国实验方剂学杂志,2012,18(4):10-12
7徐东伟,刘同祥.乙醇注入法制备柚皮素脂质体及其质量评价[J].中南药学,2015,13(12):1266-1269
8温思菁,陈家乐,管咏梅,等.马钱子总碱脂质体凝胶的制备及其体外透皮作用[J].中国医院药学杂志,2017,37(1):36-39
9曹佳薇,倪坚军,姚君,等.利福平脂质体温敏型原位凝胶的制备及其体外释药特征研究[J].中国现代应用药学,2016,33(2):183-187
10李秀英,曾凡,赵曜.脂质体药物递送系统的研究进展[J].中国新药杂志,2014,23(16):1904-1917
2李思思,张洪兵,朱雪瑜.高乌甲素新型制剂的研究进展[J].现代药物与临床,2014,29(7):818-823
3侯丽芬,谷克仁,吴永辉.不同制剂脂质体制备方法的研究进展[J].河南工业大学学报,2016,37(5):118-124
4 Lin L,Zhu Y,Thangaraj B,et al.Improving the stability of thyme essential oil solid liposome by usingβ-cyclodextrin as a cryoprotectant[J].Carbohydrate Polymers,2018,188:243-251
5付金芳,曹伶俐,李乘欣,等.氢溴酸高乌甲素纳米粒缓释片的制备[J].中成药,2017,39(5):952-955
6张晓丽,吴品昌,刘宇,等.乙醇注入法制备莪术醇脂质体[J].中国实验方剂学杂志,2012,18(4):10-12
7徐东伟,刘同祥.乙醇注入法制备柚皮素脂质体及其质量评价[J].中南药学,2015,13(12):1266-1269
8温思菁,陈家乐,管咏梅,等.马钱子总碱脂质体凝胶的制备及其体外透皮作用[J].中国医院药学杂志,2017,37(1):36-39
9曹佳薇,倪坚军,姚君,等.利福平脂质体温敏型原位凝胶的制备及其体外释药特征研究[J].中国现代应用药学,2016,33(2):183-187
10李秀英,曾凡,赵曜.脂质体药物递送系统的研究进展[J].中国新药杂志,2014,23(16):1904-1917