外用皮質類固醇臨床上常用來治療不同的皮膚炎症。本論文研究Hydrocortisone acetate於軟膏基劑中之化學穩定性，藉由不同單一基劑和高溫環境等條件下的安定性測試，探討其不安定之因素。此外，利用高效液相層析儀，建立一個分析方法，提供業界在製程上進行有效的品質管制。 本次選用四種常用基劑，包含水、水溶型(聚乙二醇PEG400和丙二醇)及烴類(凡士林油)基質，藉由置於60℃溫度的環境，經過測試後，對其性狀、含量作化學性評估。定量分析選用高效液相層析法，由實驗結果得知，HCA於在60℃下，對水和凡士林油幾乎不溶、微溶於PEG400及PG。 藥品於飽和情況下，溶解的量越多則降解速率越大；在未飽和情況下，則可以使用一階次動力模式分析且基劑影響程度為PG>PEG400>水>油。其中PEG跟PG對於HCA來說是不安定的，若需使用得仔細考慮處方及用量。由飽和情況與未飽和情況比較結果，若藥品在外用能做成懸液劑的情況則有機會延長藥品安定性。 Topical steroid preparations are applied in treatment for diverse skin diseases clinically. In this thesis, the chemical stability of hydrocortisone acetate (HCA) in ointment bases was studied. By means of stability tests of different bases dissolving HCA with high temperature, we want to figure out what makes hydrocortisone acetate (HCA) instable at liquid state. Besides, while operating high performance liquid chromatography (HPLC), an analytic method had been developed, offers a way for drug industry at qualitative control. There were 4 common bases being chosen, including water, water-washable (PEG 400 and PG), and oil vehicles. All of them were under 60℃ temperature conditions. Then, we evaluated their physical and chemical properties. HPLC was used for analysis the content of HCA. At 60℃ temperature, HCA is practically insoluble with water and Vaseline oil, while it is slightly soluble in PEG400 and PG. Higuchi model can be described for the kinetic of degradation of HCA at saturated state in vehicles. The more amounts of HCA dissolved in vehicles, the degradation rate is larger. A first-order model was fitting to an unsaturated state. As HCA is unstable in PEG400 and PG, it’s important to think carefully on formulation with pharmaceuticals, because the influence level of vehicles affect in HCA: PG>PEG400>water>oil. In summary, we concluded that the recommended dosage form of HCA is made of suspension after comparing the saturated and unsaturated state for prolonging the stability.
