在水性环氧德克斯眼部制剂中的他类药物的化学稳定性表征和动力学:一种配方观点
Ismael Abo Horan1, Thorsteinn Loftsson1, Hakon Hrafn Sigurdsson1
1Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland.
Pharmaceutics
|July 30, 2025
概括
循环德克斯特林 (CD) 可以改善局部他类眼滴,但pH和CD的选择至关重要. RMβCD稳定了他类药物,而γ-CD和HPβCD加速了水解,影响了药物的稳定性.
科学领域:
- 制药科学 制药科学
- 眼科医生 眼科 眼科
- 药物运输 药物运输 药物运输
背景情况:
- 局部他类药物治疗显示了与年龄相关的黄斑变性等眼部疾病的潜力.
- 由于水溶性差,化学不稳定性和眼壁障碍,有效的输送到眼睛后部段受到阻碍.
- 环极素 (CDs) 可以提高溶解性和稳定性,但它们对眼滴中乳/酸平衡的影响尚不清楚.
研究的目的:
- 为了研究环德素 (CD) 度和类型对simvastatin和atorvastatin的乳/酸平衡的影响.
- 定义配方参数,包括他类药物形式,CD类型和度以及pH值,以实现稳定的眼滴发育.
主要方法:
- 西姆瓦斯塔丁或阿托瓦斯塔丁在缓冲溶液 (pH2.0-9.5) 中与各种环极素 (RMβCD,HPβCD,γ-CD,SBEβCD) 化,度为0%,5%和10%.
- 使用UPLC量化乳和酸形式的时间,并计算速率常数.
- 进行相位溶解性研究以描述平衡行为.
主要成果:
- 类药物的乳形式在pH 4.5时最稳定;酸形式在pH ≥ 7时占主导地位.
- γ-CD和HPβCD加速了乳水解,而RMβCD表现出稳定作用.
- 将CD度从5%提高到10%,提供了最小的额外稳定性.
结论:
- 精确的pH控制对于开发化学稳定的他类眼滴至关重要.
- 选择环极素显著影响他类药物的稳定性,RMβCD是一个有前途的选择.
- 选择合适的他类药物形式对于成功的眼滴配方至关重要.
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