积雪草苷微乳凝胶的制备与体外透皮研究
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摘要
目的制备积雪草苷微乳凝胶,并考察其体外透皮性能。方法考察积雪草苷在不同油、乳化剂、助乳化剂中的平衡溶解度,通过伪三元相图法最终确定积雪草苷微乳的处方组成;分别以玉米油、Smix、水作为考察因素,以形成微乳的平均粒径作为评价指标,利用单纯网格实验设计优化积雪草苷微乳的处方;在透射电镜下观察积雪草苷微乳的微观形态,测定粒径分布、PDI及Zeta电位;以卡波姆940为基质制备积雪草苷微乳凝胶,并采用Franz扩散池法考察了积雪苷霜软膏、微乳及微乳凝胶的体外透皮吸收性能。结果优选积雪草苷微乳的处方组成为:玉米油为15. 2%、Smix为66. 2%、水为18. 6%;透射电镜下观察到积雪草苷微乳呈圆整、规则球形,粒径分布较为均匀,平均粒径为57. 8±3. 6nm,PDI为0. 172±0. 03,Zeta电位为-19. 6±0. 9 m V;积雪草苷微乳和微乳凝胶在12 h时内的药物累积透皮量显著高于积雪苷霜软膏,皮肤内药物滞留量分别是积雪苷霜软膏的3. 3、6. 7倍。结论积雪草苷微乳凝胶可以显著增加药物的累积透皮量,提高药物在皮肤中的滞留量,有望成为积雪草苷的新型局部给药制剂。
OBJECTIVE To prepare the asiaticoside loaded microemulsion-based gel and to investigate its transdermaldelivery in vitro. METHODS The solubility of asiaticoside in different oils,emulsifiers and co-emulsifiers was investigated byequilibrium solubility experiments. The formulation composition of asiaticoside microemulsion was determined by Pseudo-ternaryphase diagram. By setting the average particle size as dependent variables whilst corn oil,Smix and water as the independentvariables,a Simplex Lattice experiment design was used to optimize the asiaticoside loaded microemulsion formulation. Themicroscopic morphology of asiaticoside loaded microemulsion was observed by transmission electron microscopy,and the particlesize distribution,Pd I and Zeta potential were determined. The asiaticoside loaded microemulsion-based gel was prepared withCarbomer 940 as a matrix. The in vitro transdermal absorption properties of asiaticoside cream,asiaticoside loaded microemulsionand microemulsion-based gel were investigated by Franz diffusion cell method. RESULTS The composition of the asiaticosidemicroemulsion was as follows:corn oil was 15. 2%;Smix was 66. 2% and water was 18. 6%. Under the transmission electronmicroscope,the asiaticoside microemulsion was round and regular spherical,and the particle size distribution was uniform. Theaverage particle size was 57. 8 ± 3. 6 nm,PDI was 0. 172 ± 0. 013 and Zeta potential was-19. 6 ± 0. 9 m V. The drugaccumulation transdermal amount of asiaticoside microemulsion and the microemulsion-based gel were significantly higher thanthat of asiaticoside cream after 12 h. The drug retention in the skin were 3. 3 and 6. 7 fold of asiaticoside cream,respectively.CONCLUSION Asiaticoside loaded microemulsion-based gel can significantly increase the cumulative transdermal deliveryof drugs and increase the retention of drugs in the skin. It is expected to be a novel vehicle for the topical use of asiaticoside.
OBJECTIVE To prepare the asiaticoside loaded microemulsion-based gel and to investigate its transdermaldelivery in vitro. METHODS The solubility of asiaticoside in different oils,emulsifiers and co-emulsifiers was investigated byequilibrium solubility experiments. The formulation composition of asiaticoside microemulsion was determined by Pseudo-ternaryphase diagram. By setting the average particle size as dependent variables whilst corn oil,Smix and water as the independentvariables,a Simplex Lattice experiment design was used to optimize the asiaticoside loaded microemulsion formulation. Themicroscopic morphology of asiaticoside loaded microemulsion was observed by transmission electron microscopy,and the particlesize distribution,Pd I and Zeta potential were determined. The asiaticoside loaded microemulsion-based gel was prepared withCarbomer 940 as a matrix. The in vitro transdermal absorption properties of asiaticoside cream,asiaticoside loaded microemulsionand microemulsion-based gel were investigated by Franz diffusion cell method. RESULTS The composition of the asiaticosidemicroemulsion was as follows:corn oil was 15. 2%;Smix was 66. 2% and water was 18. 6%. Under the transmission electronmicroscope,the asiaticoside microemulsion was round and regular spherical,and the particle size distribution was uniform. Theaverage particle size was 57. 8 ± 3. 6 nm,PDI was 0. 172 ± 0. 013 and Zeta potential was-19. 6 ± 0. 9 m V. The drugaccumulation transdermal amount of asiaticoside microemulsion and the microemulsion-based gel were significantly higher thanthat of asiaticoside cream after 12 h. The drug retention in the skin were 3. 3 and 6. 7 fold of asiaticoside cream,respectively.CONCLUSION Asiaticoside loaded microemulsion-based gel can significantly increase the cumulative transdermal deliveryof drugs and increase the retention of drugs in the skin. It is expected to be a novel vehicle for the topical use of asiaticoside.
引文
[1]彭琴,陈力.积雪草苷对增生性瘢痕作用机制研究进展[J].辽宁中医药大学学报,2014(3):237-239.
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[7]王杏林,尹东东,张俊伟.依托泊苷口服微乳的制备及质量评价[J].华西药学杂志,2009,24(2):139-141.
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[11]Zhang J,Michniak-Kohn B.Investigation of microemulsion microstructures and their relationship to transdermal permeation of model drugs:Ketoprofen lidocaine,and caffeine[J].Int J Pharm,2011,421(1):34-44.
[12]Hathout RM,Nasr M.Transdermal delivery of betahistine hydrochloride using microemulsions:Physical characterization,biophysical assessment,confocal imaging and permeation studies[J].Colloids Surf B Biointerfaces,2013,110:254-260.
[13]邢建国,赵媛,王新春,等.不同基质对复方卡力孜然凝胶剂主要活性成分体外透皮吸收的影响[J].中成药,2011,33(10):1718-1721.
[2]梁李广,马维.HPLC测定不同产地和不同时间的积雪草中的积雪草苷和羟基积雪草苷[J].华西药学杂志,2009,24(2):186-187.
[3]张阳阳,陈莉,张莉,等.积雪草苷平衡溶解度和油水分配系数的测定[J].解放军药学学报,2013,29(3):189-191.
[4]孙进.现代药物制剂技术丛书-口服药物吸收与转运[M].北京:人民卫生出版社,2006:345-346.
[5]Sabale V,Vora S.Formulation and evaluation of microemulsion-based hydrogel for topical delivery[J].Int J Pharm Invest,2012,2(3):140-149.
[6]钟华,尹蓉莉,谢秀琼,等.莪术微乳凝胶的成型工艺研究[J].华西药学杂志,2010,25(5):523-526.
[7]王杏林,尹东东,张俊伟.依托泊苷口服微乳的制备及质量评价[J].华西药学杂志,2009,24(2):139-141.
[8]Sahoo S,Pani N R,Sahoo S K.Microemulsion based topical hydrogel of sertaconazole:Formulation,characterization and evaluation[J].Colloids Surf B Biointerfaces,2014,120:193-199.
[9]Zhu W,Yu A,Wang W.Formulation design of microemulsion for dermal delivery of penciclovir[J].Int J Pharm,2008,360(1-2):184-190.
[10]Khurana S,Jain NK,Bedi PM.Nanoemulsion based gel for transdermal delivery of meloxicam:Physico-chemical,mechanistic investigation[J].Life Sci,2013,92(6-7):383-392.
[11]Zhang J,Michniak-Kohn B.Investigation of microemulsion microstructures and their relationship to transdermal permeation of model drugs:Ketoprofen lidocaine,and caffeine[J].Int J Pharm,2011,421(1):34-44.
[12]Hathout RM,Nasr M.Transdermal delivery of betahistine hydrochloride using microemulsions:Physical characterization,biophysical assessment,confocal imaging and permeation studies[J].Colloids Surf B Biointerfaces,2013,110:254-260.
[13]邢建国,赵媛,王新春,等.不同基质对复方卡力孜然凝胶剂主要活性成分体外透皮吸收的影响[J].中成药,2011,33(10):1718-1721.