甲氨蝶呤磷脂复合物有机凝胶的制备、表征及透皮行为考察  

Preparation,Characterization and Transdermal Behavior of Methotrexate Phospholipid Complex Organogel

作　　者：王宝娟 刘璐瑶 盛建伟 胡君萍[2] 周文虎 WANG Baojuan;LIU Luyao;SHENG Jianwei;HU Junping;ZHOU Wenhu(Pharmaceutical Department of the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China;China Quality Mark Certification(Shandong)Co.,Ltd.,Jinan 250100,China;Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410006,China;Xinjiang Key Laboratory of Clinical Drug Research,Urumqi 830011,China)

机构地区：[1]新疆医科大学第一附属医院药学部,乌鲁木齐830011 [2]新疆医科大学药学院,乌鲁木齐830017 [3]方圆标志检验检测(山东)有限公司,济南250100 [4]中南大学湘雅药学院,长沙410006 [5]新疆药物临床研究重点实验室,乌鲁木齐830011

出　　处：《中国药学杂志》2025年第6期630-637,共8页Chinese Pharmaceutical Journal

摘　　要：目的 制备甲氨蝶呤磷脂复合物有机凝胶(methotrexate phospholipid complex organogel, MTX-PC/OG),并表征及考察其透皮行为。方法 以甲氨蝶呤磷脂复合物(MTX-PC)在油相中的溶解度、最低成胶浓度、相转变温度及稳定性为评价指标,初步筛选MTX-PC/OG的油相种类、胶凝剂及辅助胶凝剂的种类与用量;以离体乳猪皮肤为渗透屏障,采用改良Franz扩散池法,考察油相种类、辅助胶凝剂种类及用量对MTX-PC体外透皮行为的影响。并对MTX-PC/OG的外观性状、黏度、相转变温度、含量及流变学性质进行表征。结果 中链甘油三酯(medium chain triglyceride, MCT)、肉豆蔻酸异丙酯(isopropyl myristate, IPM)、油酸乙酯(ethyl oleate, EO)3种油相对MTX-PC溶解性均较好,单硬脂酸甘油酯(GMS)作为胶凝剂时成胶能力最强,用量为12.5%时,凝胶涂展性佳;体外经皮渗透结果显示,以MCT为油相,司盘20(Span 20)为辅助胶凝剂促进MTX渗透和滞留的作用最为显著。MTX-PC/OG呈淡黄色半固体状态,均匀细腻,黏度为(85.9±0.5) Pa·s,相转变温度为(50.4±0.5)℃;流变学结果表明MTX-PC/OG为假塑性流体,具有剪切稀化效应,利于涂展。结论 MTX-PC/OG处方工艺合理,具有良好的透皮和流变性能,适于皮肤局部给药。OBJECTIVE To prepare,characterize,and investigate the transdermal behavior of methotrexate phospholipid complex organogel(MTX-PC/OG).METHODS The solubility of MTX-PC in the oil phase,lowest gelling concentration,phase transition temperature,and stability were evaluated as criteria.Preliminary screening of oil phase types,gelling agents,and types and amounts of cogelators for MTX-PC/OG was carried out.The effects of oil phase type,cogelator type and dosage on the transdermal behavior of MTX-PC in vitro were investigated by modified Franz diffusion cell method.The appearance,viscosity,phase transition temperature,content and rheological properties of MTX-PC/OG were characterized.RESULTS Medium chain triglyceride(MCT),isopropyl myristate(IPM)and ethyl oleate(EO)exhibited favorable solubility for MTX-PC.Glycerin monostearate(GMS)demonstrated the most robust gelling capacity as a gelling agent,with optimal gel spreading at a 12.5%concentration.In vitro transdermal permeation results indicated that using MCT as the oil phase and Span 20 as the cogelator significantly enhanced MTX permeation and retention.MTX-PC/OG appeared as a light yellow semisolid state with a uniform texture,viscosity of(85.9±0.5)Pa·s,and a phase transition temperature of(50.4±0.5)℃.Rheological assessments revealed that MTX-PC/OG is a pseudoplastic fluid with shear-thinning effects,suitable for transdermal drug delivery.Rheological assessments revealed that MTX-PC/OG is a pseudoplastic fluid with shear-thinning effects that facilitate its easy spread.CONCLUSION MTX-PC/OG prescription process is reasonable,with good transdermal and rheological behavior,making it well-suited for skin topical drug delivery.

关 键 词：甲氨蝶呤 磷脂 有机凝胶 透皮性能 表征 流变学特性 

分 类 号：R944[医药卫生—药剂学]