雌二醇透皮喷雾成膜剂的研制及其体外评价

Development and in vitro evaluation of estradiol transdermal film-forming spray

为了开发雌二醇的透皮喷雾成膜剂,以溶液外观、喷雾性能、成膜速度和外观为指标,筛选了适于制备透皮喷雾成膜剂的聚合物。以乳猪皮肤为模型,考察了聚合物、增塑剂和促渗剂对药物透皮速率的影响,并与商品化的雌二醇贴剂和凝胶比较。使用差示扫描量热法(DSC)考察药物在相变型透皮喷雾剂所成膜中的存在状态。Eudragit E PO、RL PO、羟丙基纤维素EF、聚乙烯吡咯酮K30、Plasdone S630、Agrimer VA64的溶液外观、喷雾性能、成膜速度和外观均符合要求,可以用于制备透皮喷雾成膜剂。雌二醇在以Eudragit RL PO制备的制剂中透皮速率最高;增塑剂柠檬酸三乙酯使透皮速率降低;促渗剂油酸、肉豆蔻酸异丙酯和薄荷醇使雌二醇的透皮速率降低,月桂氮酮使雌二醇的透皮速率增加。透皮喷雾成膜剂的透皮速率和24 h累积透过量均高于贴剂和凝胶。DSC结果表明雌二醇以分子的形式存在于透皮喷雾成膜剂给药后所形成的薄膜中。提示透皮喷雾成膜剂有望成为高效的透皮制剂。

To develop estradiol transdermal film-forming spray （TFS）, various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry （DSC）. The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone $630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.