Saito Jumpei, Yoshikawa Nozomi, Hanawa Takehisa, Ozawa Ayuna, Matsumoto Takahiro, Harada Tsutomu, Iwahashi Kana, Nakamura Hidefumi, Yamatani Akimasa
Department of Pharmacy, National Center for Child Health and Development, Setagaya-ku, Tokyo 157-0054, Japan.
Division of Clinical Pharmacology and Oral Formulation Development, National Center for Child Health and Development, Tokyo 157-0054, Japan.
Pharmaceutics. 2021 Aug 17;13(8):1267. doi: 10.3390/pharmaceutics13081267.
Hydrocortisone has been utilized in the management of adrenal insufficiency. For pediatric patients, the commercially available enteral form of hydrocortisone tablets (Cortoril) is administered in powder form after being compounded by a pharmacist. However, the stability and quality of compounded hydrocortisone powder have not been verified. In this study, we formulated a 20 mg/g oral hydrocortisone powder by adding lactose monohydrate to crushed and filtered hydrocortisone tablets and assessed the stability and physical properties of this compounded product in polycarbonate amber bottles or coated paper packages laminated with cellophane and polyethylene. Stability was examined over 120 days in three storage conditions: closed bottle, in-use bottle, and laminated paper. Drug dissolution and powder X-ray diffraction analysis were conducted to assess its physicochemical stabilities. Validated liquid chromatography-diode array detection was used to detect and quantify hydrocortisone and its degradation products. Although impurity B (cortisone) and G (hydrocortisone-21-aldehyde) were found after 120 days of storage, no crystallographic and dissolution changes were noted. Hydrocortisone content was maintained between 90% and 110% of initial contents for 120 days at 25 ± 2 °C and 60 ± 5% relative humidity in all packaging conditions.
氢化可的松已被用于治疗肾上腺功能不全。对于儿科患者，市售的氢化可的松片剂（可的索）肠溶制剂经药剂师配制后以粉末形式给药。然而，配制的氢化可的松粉末的稳定性和质量尚未得到验证。在本研究中，我们通过向粉碎并过滤后的氢化可的松片剂中添加一水乳糖，配制了一种20 mg/g的口服氢化可的松粉末，并评估了该配制产品在聚碳酸酯琥珀色瓶或用玻璃纸和聚乙烯层压的涂层纸包装中的稳定性和物理性质。在三种储存条件下（密闭瓶、使用中瓶和层压纸），对其稳定性进行了120天的考察。进行了药物溶出度和粉末X射线衍射分析，以评估其物理化学稳定性。采用经过验证的液相色谱 - 二极管阵列检测法来检测和定量氢化可的松及其降解产物。尽管在储存120天后发现了杂质B（可的松）和G（氢化可的松 - 21 - 醛），但未观察到晶体学和溶出度的变化。在所有包装条件下，在25±2°C和60±5%相对湿度下，氢化可的松含量在120天内保持在初始含量的90%至110%之间。
