Box-Behnken响应面法优化哈西奈德脂质体的制备工艺
|
摘要
目的采用Box-Behnken响应面法优化哈西奈德脂质体制备工艺。方法考察哈西奈德∶磷脂(质量比)、胆固醇∶磷脂(质量比)、VE∶磷脂(质量比)、乙醇用量等因素对哈西奈德脂质体包封率的影响;采用Box-Behnken响应面法优化哈西奈德脂质体制备工艺;并对脂质体的形态、粒径及透皮性能进行评价。结果哈西奈德脂质体优化工艺为:哈西奈德∶磷脂(质量比)为2.1∶10;胆固醇∶磷脂(质量比)为1.9∶10;VE∶磷脂(质量比)为0.4∶10;乙醇用量为4.66 mL,预测包封率达81.95%,实际包封率为79.25%,偏差较小,预测性良好。在最优化制备工艺条件下,哈西奈德脂质体的粒径为(148.2±10.3)nm、Zeta电位为41.67 mV,2、4、6、8、10、12 h的累积透过量和累积渗透率均显著高于哈西奈德溶液组(P<0.01)。结论 Box-Behnken响应面法可以准确快速地优化哈西奈德脂质体的制备工艺,哈西奈德脂质体具有良好的透皮性能。
Objective To optimize the preparation process of the Hasinide liposomes by the Box-Behnken response surface methodology. Methods The effects of Hassinide∶phospholipid ratio,cholesterol∶phospholipid ratio,VE∶phospholipid ratio,ethanol dosage on encapsulation efficiency of Hassinide liposomes were investigated. Box-Behnken response surface methodology was used to optimize the preparation of Hassinide liposomes. The morphology,particle size and transdermal properties of liposomes were evaluated. Results The optimum technology of Hassinide liposomes was as follows: Hassinide∶phospholipid ratio was 2.1∶10; cholesterol∶ phospholipid ratio was 1.9∶10; VE∶phospholipid ratio was 0.4∶10; ethanol dosage was 4.66 mL,the predicted encapsulation rate was 81.95%,the actual encapsu-lation rate was 79.25%,the deviation was small,and the predictability was good. Under the optimum preparation conditions,the particle size of Hassinide liposomes was(148.2+10.3) nm and Zeta potential was 41.67 mV. The cumulative transdermal amounts at 2,4,6,8,10 and 12 h and cumulative permeability of Hassinide liposomes were significantly higher than those of Hassinide solution group(P<0.01).Conclusions Box-Behnken response surface methodology can accurately and rapidly optimize the preparation process of Hassinide liposomes. The Hasinide liposomes have good transdermal properties.
Objective To optimize the preparation process of the Hasinide liposomes by the Box-Behnken response surface methodology. Methods The effects of Hassinide∶phospholipid ratio,cholesterol∶phospholipid ratio,VE∶phospholipid ratio,ethanol dosage on encapsulation efficiency of Hassinide liposomes were investigated. Box-Behnken response surface methodology was used to optimize the preparation of Hassinide liposomes. The morphology,particle size and transdermal properties of liposomes were evaluated. Results The optimum technology of Hassinide liposomes was as follows: Hassinide∶phospholipid ratio was 2.1∶10; cholesterol∶ phospholipid ratio was 1.9∶10; VE∶phospholipid ratio was 0.4∶10; ethanol dosage was 4.66 mL,the predicted encapsulation rate was 81.95%,the actual encapsu-lation rate was 79.25%,the deviation was small,and the predictability was good. Under the optimum preparation conditions,the particle size of Hassinide liposomes was(148.2+10.3) nm and Zeta potential was 41.67 mV. The cumulative transdermal amounts at 2,4,6,8,10 and 12 h and cumulative permeability of Hassinide liposomes were significantly higher than those of Hassinide solution group(P<0.01).Conclusions Box-Behnken response surface methodology can accurately and rapidly optimize the preparation process of Hassinide liposomes. The Hasinide liposomes have good transdermal properties.
引文
[1] SUDILOVSKY A,CLEWE T H.Comparative efficacy of halcino-nide and fluocinonide creams in psoriasis and eszematous dermatoses[J].J Clin Pharmacol,2013,15(11/12):779-784.
[2] DRAELOS Z D.Demonstration of the biphasic release of 0.1% halcinonide cream[J].J Drugs Dermatol,2015,14(1):89-90.
[3] 兰颐.萜烯类经皮促透剂对皮肤活性表皮层的影响及其机制研究[J].中国中药杂志,2015,40(4):643-648.
[4] BOZZUTO G,MOLINARI A.Liposomes as nanomedical devices[J].Int J Nanomed,2015,10(default):975-999.
[5] KWON S S,KIM S Y,KONG B J,et al.Cell penetrating peptide conjugated liposomes as transdermal delivery system of Polygonum aviculare L.extract[J].Int J Pharmaceut,2015,483(1/2):26-37.
[6] 李志平,梁庆,刘文彬,等.哈西奈德脂质体制备方法的选择及其含量与包封率的测定[J].今日药学,2011,21(6):332-334.
[7] 王学艳,崔飙.HPLC法测定牛皮癣乳膏中维A酸和哈西奈德的含量[J].中国药房,2007,18(22):1740-1741.
[8] 王敏,林茂,邓英杰,等.盐酸丁卡因脂质体凝胶皮肤刺激性实验及药效[J].遵义医学院学报,2015,38(6):599-603.
[9] 杨静文,邓英杰,任雁,等.维甲酸脂质体在小鼠体内的药物动力学及组织分布[J].沈阳药科大学学报,2007,24(12):731-735.
[10] 肖艳,李雪芽,曾抗.不同剂型鬼臼毒素治疗尖锐湿疣的研究进展[J].中国皮肤性病学杂志,2013,27(5):524-525.
[11] 郑雪花,于黎鹏,杨君,等.氢化可的松角质类脂质体的理化性质及其体外经皮渗透研究[J].中国新药杂志,2017,26(15):1822-1826.
[12] 涂名扬,陈超,王淑美,等.D-最优设计响应面法优选芪枣口服液提取工艺[J].广东药科大学学报,2017,33(1):33-36.
[13] 谢郁峰,陈日佳,严春艳.响应面法优化番石榴叶总黄酮的超声提取工艺[J].广东药学院学报,2014,30(4):417-421.
[14] 黄梓源,孙玉琦,胡海洋,等.脂质体制剂学稳定性的研究技术与方法[J].药学学报,2016(3):356-361.
[15] 郑钦,陶静,张亦斌,等.盐酸吉西他滨隐形脂质体的制备及工艺优化[J].中国抗生素杂志,2017,42(5):382-388.
[2] DRAELOS Z D.Demonstration of the biphasic release of 0.1% halcinonide cream[J].J Drugs Dermatol,2015,14(1):89-90.
[3] 兰颐.萜烯类经皮促透剂对皮肤活性表皮层的影响及其机制研究[J].中国中药杂志,2015,40(4):643-648.
[4] BOZZUTO G,MOLINARI A.Liposomes as nanomedical devices[J].Int J Nanomed,2015,10(default):975-999.
[5] KWON S S,KIM S Y,KONG B J,et al.Cell penetrating peptide conjugated liposomes as transdermal delivery system of Polygonum aviculare L.extract[J].Int J Pharmaceut,2015,483(1/2):26-37.
[6] 李志平,梁庆,刘文彬,等.哈西奈德脂质体制备方法的选择及其含量与包封率的测定[J].今日药学,2011,21(6):332-334.
[7] 王学艳,崔飙.HPLC法测定牛皮癣乳膏中维A酸和哈西奈德的含量[J].中国药房,2007,18(22):1740-1741.
[8] 王敏,林茂,邓英杰,等.盐酸丁卡因脂质体凝胶皮肤刺激性实验及药效[J].遵义医学院学报,2015,38(6):599-603.
[9] 杨静文,邓英杰,任雁,等.维甲酸脂质体在小鼠体内的药物动力学及组织分布[J].沈阳药科大学学报,2007,24(12):731-735.
[10] 肖艳,李雪芽,曾抗.不同剂型鬼臼毒素治疗尖锐湿疣的研究进展[J].中国皮肤性病学杂志,2013,27(5):524-525.
[11] 郑雪花,于黎鹏,杨君,等.氢化可的松角质类脂质体的理化性质及其体外经皮渗透研究[J].中国新药杂志,2017,26(15):1822-1826.
[12] 涂名扬,陈超,王淑美,等.D-最优设计响应面法优选芪枣口服液提取工艺[J].广东药科大学学报,2017,33(1):33-36.
[13] 谢郁峰,陈日佳,严春艳.响应面法优化番石榴叶总黄酮的超声提取工艺[J].广东药学院学报,2014,30(4):417-421.
[14] 黄梓源,孙玉琦,胡海洋,等.脂质体制剂学稳定性的研究技术与方法[J].药学学报,2016(3):356-361.
[15] 郑钦,陶静,张亦斌,等.盐酸吉西他滨隐形脂质体的制备及工艺优化[J].中国抗生素杂志,2017,42(5):382-388.