摘要
目的测定睾酮(testosterone,TS)的平衡溶解度、油水分配系数等理化性质,考察促透剂对其体外经皮渗透特性的影响,以指导用于女性性功能障碍治疗的睾酮涂膜剂研发工作。方法建立含量测定方法,测定睾酮在9种介质中的平衡溶解度及油水分配系数;采用体外改良扩散池法,以药物累计渗透量(Q)、经皮渗透速率(Js)、滞后时间(t)及增渗比(ER)为评价指标,考察6种促透剂对其经皮吸收的促进作用。结果睾酮在水相介质中溶解度小,PEG400可增溶作为扩散池接收介质;lg P值为3.7,为典型脂溶性药物。质量分数5%肉豆蔻酸异丙酯(IPM)的体外经皮渗透作用最为显著,增透倍数可达2.43倍,但其滞后时间相对较长;溶解能力与促透能力排序无规律性关联。结论睾酮适于构建经皮给药系统,促透剂的应用可在不同程度上影响其皮肤渗透性(提高或降低),其溶解药物能力与促透能力不成正比,以上结果可为涂膜剂处方设计提供实验基础。
Objective To evaluate the equilibrium solubility, oil-water partition coefficient and other physico- chemical properties of testosterone （TS） in order to guide the development of TS plastics which is used to treat sexual dysfunction. The behavior of TS percutaneous permeability was also investigated by using differ- ent penetration enhancers at present study. Methods The assay method of TS was established, and equilibri- um solubility and oil-water partition coefficient of TS in 9 different mediums were determined. In vitro modi- fied Franz diffusion cell method was used to investigate the effect of transdermal absorption of six penetra- tion enhancers with the evaluating index of accumulated amount permeated （ Q）, steady penetration rate （Js）, lag time （t） and enhancing rate （ER）. Results The solubility of TS was small in most aqueous medi- ums and which could be increased by adding PEG400 into the receptor solution of the diffusion cell. The lgP value of TS was 3.7, indicating TS was the typical lipophilic drug. Isopropyl myristate （IPM） was observed to provide the most significant enhancement for the percutaneous permeability of TS. The enhanced permea- bility was 2.43 times compared with the drug, while the lag time was relatively longer. The dissolving capac- ity was irrelevant to the penetration ability. Conclusions testosterone is suitable for transdermal drug delivery system（TDDS）. The penetration enhancers can affect the permeability of the skin, either improving or de- creasing. The dissolving capacity is not proportional to the penetration ability. The above results provide the experimental basis for the design of the plastics formulation.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2014年第6期428-434,共7页
Journal of Shenyang Pharmaceutical University
基金
上海市人口和计划生育委员会局管科技发展基金资助项目(2010JG08)
关键词
睾酮
平衡溶解度
油水分配系数
经皮渗透特性
促透剂
testosterone
equilibrium solubility
oil-water partition coefficient
percutaneous permeability
penetration enhancer
