高乌甲素脂质体凝胶制备工艺及体外释药性能研究
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摘要
目的:制备高乌甲素脂质体(LA-LIP)经皮给药制剂,对其质量及透皮吸收性质进行考察。方法:采用薄膜分散法制备LA-LIP,以包封率与载药量为指标,运用正交试验法确定LA-LIP的优选处方;以卡波姆-940为基质制备LA-LIP凝胶,采用体外释放试验评估释放能力。结果:正交试验法确定LA-LIP最佳处方工艺组合为卵磷脂与胆固醇质量比为8∶1、药脂比为1∶8、水化温度为55℃。体外透析袋实验显示,LA-LIP凝胶慢释过程符合Higuchi方程,LA凝胶释放过程符合零级动力学方程;体外透皮结果显示,LA凝胶24 h内皮肤滞留量为8.39μg·cm~(-2),LA-LIP凝胶皮肤滞留量为15.17μg·cm~(-2)。结论:本研究发现运用薄膜分散法制备LA-LIP工艺简单可靠,制备成脂质体凝胶剂时,具有缓释效果。
OBJECTIVE To prepare the percutaneous preparations of lappaconitine liposomes(LA-LIP) and investigate its quality and transdermal absorption properties. METHODS LA-LIP was prepared by thin film dispersion method. The optimal formulation of LA-LIP was determined by orthogonal test using encapsulation rate and drug loading as indicators. LA-LIP gel was prepared using carbopol-940 as matrix and the release capacity was evaluated by in vitro release assay.RESULTS Orthogonal test method was used to determine the best prescription combination of lappaconitine liposomes:lecithin:cholesterol=8∶1, drug-to-lipid ratio 1∶8, hydration temperature 55 ℃. In vitro dialysis bag experiment shows that the LA-LIP gel slow release process conforms to the Higuchi equation and the LA gel release process conforms to the zero-order equation. In vitro transdermal results suggested that the retention volume of LA gel within 24 hours was 8.39 μg·cm~(-2), and that of LA-LIP gel was 15.17 μg·cm~(-2). CONCLUSION In the current study, it was found that the preparation of LA-LIP by film dispersion method is simple and reliable. When it is prepared as a liposome gel, it has a sustained-release effect.
OBJECTIVE To prepare the percutaneous preparations of lappaconitine liposomes(LA-LIP) and investigate its quality and transdermal absorption properties. METHODS LA-LIP was prepared by thin film dispersion method. The optimal formulation of LA-LIP was determined by orthogonal test using encapsulation rate and drug loading as indicators. LA-LIP gel was prepared using carbopol-940 as matrix and the release capacity was evaluated by in vitro release assay.RESULTS Orthogonal test method was used to determine the best prescription combination of lappaconitine liposomes:lecithin:cholesterol=8∶1, drug-to-lipid ratio 1∶8, hydration temperature 55 ℃. In vitro dialysis bag experiment shows that the LA-LIP gel slow release process conforms to the Higuchi equation and the LA gel release process conforms to the zero-order equation. In vitro transdermal results suggested that the retention volume of LA gel within 24 hours was 8.39 μg·cm~(-2), and that of LA-LIP gel was 15.17 μg·cm~(-2). CONCLUSION In the current study, it was found that the preparation of LA-LIP by film dispersion method is simple and reliable. When it is prepared as a liposome gel, it has a sustained-release effect.
引文
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[16] Wu WY,Li S,Xu XN,et al.Study on stability and release rate in vitro of matrine liposome [J].China Pharm(中国药房),2013,24(37):3542-3544.
[17] Wen SJ,Chen JL,Guan YM,et al.Preparation and in vitro transdermal diffusion characteristics of liposomes gel containing total alkaloids from seed of Strychnosnux-vomic L [J].Chin Hosp Pharm J(中国医院药学杂志),2017,37(1):36-39.
[18] Shen LP,Yan DX,Zhao SK,et al.Preparation and evaluation of emodin liposomes mixed with different forms of PEG [J]. Chin Hosp Pharm J(中国医院药学杂志),2017,37(2):121-125.
[2] Li XL,Luan J,Wang H,et al.In vitro percutaneous absorption of lappaconitine micromulsion [J].Chin J Exp Tradit Med Form(中国实验方剂学杂志),2012,18(10):52-54.
[3] Zhu XC,Ge CT,Wang P,et al.Analgesic effects of lappaconitine in leukemia bone pain in a mouse model [J]. Peer J,2015,3:e936.
[4] Guo T,Zhang YT,Zhao JH,et al.Nanostructured lipid carriers for percutaneous administration of alkaloids isolated from Aconitum sinomontanum [J].J Nanobiotechnol,2015,13 (1):47.
[5] Yu LP,Yang J,Yang YH.Research progress of transdermal liposomes [J].Pract Pharm Clin Remedies(实用药物与临床),2014,17(2):217-221.
[6] Hou LF,Gu KR,Wu YH.Research progress on preparation methods of different preparation liposomes [J].J Henan Univ Technology (Natural Science)(河南工业大学学报自然科学版),2016,37(5):118-124.
[7] Tian JX,Xie Y,Yang YH.Preparation of BMPs' magnetic liposomes by film dispersion-ultrasonic method [J].Health Res(健康研究),2012(2):258-260.
[8] Zhang Y,Zhao Y,Ye XL,et al.Optimization of preparation process of brain-targeted paclitaxel liposomes [J].J Jiaying Univ(嘉应学院学报),2016,34(5):57-62.
[9] Guan YY,Li GM,Shao W.Preparation and evaluation of propranolol hydrochloride liposome gel [J]. Chin J Pharm Biotec(药物生物技术),2014,21(6):525-529.
[10] Zheng HS,Huang SW,Li FZ,et al.Preparation technology of sinomenine hydrochloride liposomes [J].Chin Tradit Herb Drugs(中草药),2013,44(4):408-413.
[11] Cao JW,Ni JJ,Yao J,et al.Preparation of rifampicin liposomes in situ gel system and its in vitro release mechanism [J]. Chin J Exp Tradit Med Form(中国实验方剂学杂志),2016,33(2):183-187.
[12] Wang JZ,Li YN,Xiong YR,et al.Preparation of oxaliplatin liposome and in vitro drug-release [J].Pharm Res(药学研究),2016,35(4):217-225.
[13] Zhu LY,Zheng GT,Zhou CN,et al.Release mechanism and preparation of liposome gel of total alkaloids of sophorasflavescentis radix [J]. Chin J Inform Tradit Chin Med(中国中医药信息杂志),2017,24(1):77-81.
[14] Zhang HH,Liu CY.Preparation and in vitro transdermal absorption of total saponins from leaves of notoginseng radix et rhizoma liposomal gels [J].Chin J Exp Tradit Med Form(中国实验方剂学杂志),2013,19(21):45-48.
[15] Zheng HS,Huang SW,Xu LY.Comparative study on drug release in vitro of integerrimine liposome and its gelling agent [J]. Chin Tradit Patent Med(中成药),2013,39(9):2027-2030.
[16] Wu WY,Li S,Xu XN,et al.Study on stability and release rate in vitro of matrine liposome [J].China Pharm(中国药房),2013,24(37):3542-3544.
[17] Wen SJ,Chen JL,Guan YM,et al.Preparation and in vitro transdermal diffusion characteristics of liposomes gel containing total alkaloids from seed of Strychnosnux-vomic L [J].Chin Hosp Pharm J(中国医院药学杂志),2017,37(1):36-39.
[18] Shen LP,Yan DX,Zhao SK,et al.Preparation and evaluation of emodin liposomes mixed with different forms of PEG [J]. Chin Hosp Pharm J(中国医院药学杂志),2017,37(2):121-125.