蟾皮凝胶剂制备工艺优选及体外透皮性能考察

Optimization of Preparation Technology of Toad Skin Gels and Investigation of Its in vitro Percutaneous Permeability

目的:优选蟾皮凝胶剂制备工艺并考察其体外透皮性能。方法:通过有效成分含量变化及药效学试验(S180腹水型荷瘤模型)筛选主药干燥方式,采用HPLC测定脂蟾毒配基、华蟾酥毒基含量,流动相乙腈-水(48∶52),检测波长296 nm。以凝胶剂外观性状考察基质种类和用量。以24 h累计渗透量(Q24 h)为指标,通过正交试验考察氮酮、丙二醇、薄荷脑用量对蟾皮凝胶制备工艺的影响,考察该凝胶剂的体外透皮性能。结果:选择冷冻干燥后蟾皮为主药,蟾皮凝胶剂处方为主药10%,羟丙基甲基纤维素K4M 2%,羟丙基甲基纤维素K100M 0.6%,薄荷脑1%,氮酮3%,丙二醇1%,甘油5%,尼泊金甲酯0.1%;脂蟾毒配基、华蟾酥毒基的Q24 h分别为3.53,8.38μg·cm-2。结论:制备的蟾皮凝胶剂外观均匀,黏度适中,涂展性好。

Objective： To optimize preparation technology of toad skin gels and investigate its in vitro transdermal performance. Method： By exterminating active ingredient content and studying pieces preliminary pharmacodynamic （S180 ascites tumor-bearing model） to screen drying process of main drug, HPLC was adopted to determine contents of resibufogenin and cinobufagin with mobile phase of acetonitrile-water （48 ： 52） and detection wavelength at 296 nm. Type and amount of matrix was investigated by observing gels appearance. With cumulative permeation amount in 24 h （Q24h） as index, orthogonal test was employed to optimize preparation technology by taking amounts of azone, propylene glycol and menthol as factors, then in vitro transdermal properties of this gels was investigated. Result： Taking toad skin after freeze dried as main drug, optimum formulation of toad skin gels was as below： main drugl0% , HPMC K4M 2% , HPMC K100M 0.6% , menthol 1% , azone 3% , propylene glycol 1% , glycerol 5% , methylparaben 0. 1% ; Q24h of resibufogenin and cinobufagin were 3.53 and 8.38 μg ·cm-2, respectively. Conclusion： These prepared toad skin gels possessed uniform appearance, moderate viscosity and good spreadability.