- 學位論文
雌二醇微乳劑凝膠之開發與評估
Development and Evaluation of Estradiol-Loaded Microemulsion-Based Gel
摘要
雌二醇(Estradiol)為一女性賀爾蒙，可用於賀爾蒙補充療法，以預防或治療因女性賀爾蒙低下所引起的症狀。然而，雌二醇雖可經由口服吸收，但極易受到胃腸道去活化作用及肝臟首渡代謝效應影響，並可能增加引起不良反應的風險。因此，改以經皮吸收的投予方式是較為適當的。 本篇研究的主要目標乃是藉由反應曲面法搭配混合實驗設計，以期能以最少實驗組數，開發最適化的雌二醇微乳劑處方，以供經皮吸收之應用，並評估處方組成成分及其比例關係對於處方性質與體外穿透試驗結果之影響。此外，更藉由聚合物的添加，進一步將微乳劑凝膠化以提升其黏度，可大幅提升製劑投予之便利性及製劑附著於皮膚的能力。 結果顯示，Carbopol系列及Pluronic系列聚合物，可以成功的開發出微乳劑凝膠劑型。而其中又以Carbopol 941具有最佳之品項外觀及較高的24小時體外累積穿透量及穿透率。與控制組相比，體外穿透累積量提高了12.0~12.5倍；與市售品相比，則為市售品之2.32~2.42倍。Flux部份，為控制組之20.0~21.3倍，為市售品之2.33~2.42倍。
並列摘要
The purpose of this study was to develop and evaluate microemulsion-based gel for topical delivery of Estradiol (E2). Estradiol is effective in treatment of postmenopause hormonal deficiency, which may lead to vasomotor flushes, atherosclerosis, and osteoporosis. However, oral administration of estradiol would be inactivated by gastrointestinal and liver first-pass metabolism effect; hence, the transdermal administration route was the most suitable for estadiol. Microemulsions are the mixtures of oil, aqueous phase, surfactant, and co-surfactant. Because of several advantages such as thermodynamic stability, optical isotropy, high solubilization capacity and easy formation, it has been widely used in recent years. In many studies, microemulsions have demonstrated a great potential for improving the systemic and local bioavailability of hydrophobic and hydrophilic therapeutic agents. However, the characteristic of low viscosity would be restricted its application. In this study, Response surface methodology was used to evaluate the effect of ingredient of the E2-loaded microemulsions on the physicochemical property and permeability, to obtain an optimal formulation with desirable goals. Then, the various gelling agents were evaluated for their potential to gel the optimal formulation of E2-loaded microemulsion. Carbopol and poloxamer series can successfully gel the E2-loaded microemulsion without affecting its structure. Compared to control group and commodity, the E2-loaded microemulsion-based gel with higher permeation rate, 20.0~21.3 fold and 2.33~2.42 fold respectively, was expected to provide effective therapeutic concentration in a workable administration.