喷雾干燥的孕激素配方用于无载体干粉吸入
Thomas Hibbard1, Hannah Mitchell1, Yoonha Kim1
1School of Pharmacy, University of Reading, Reading RG6 6AD, UK.
喷雾干燥产生可吸入的孕激素粉末,具有增强的溶解性和改善的肺部沉积. 基甲基纤维素酸糖酸盐 (HPMCAS) 是稳定孕激素配方和优化气溶性能的关键辅助剂,用于更广泛的药用应用.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 口服孕激素配方具有较低的吸收率和广泛的第一通代谢,因此需要使用替代的注射途径.
- 吸入输送为孕激素提供了一个有希望的替代品,可能绕过第一通代谢并改善生物可用性.
研究的目的:
- 通过喷雾干燥来研究吸入孕激素配方的生成.
- 评估喷雾干燥对孕激素物理化学性质的影响,包括溶解性和多态形式.
- 为了评估喷雾干燥的孕激素配方的气溶性能和肺部沉积.
主要方法:
- 用L-氨酸和基烯基甲基纤维素酸酸盐 (HPMCAS) 喷雾干燥孕激素.
- 使用X射线衍射,光谱和热分析进行表征,以确定多态形状和稳定性.
- 水溶性和超和度研究.
- 级联冲击以评估气溶性能和肺部沉积特征.
主要成果:
- 喷雾干燥始终产生的孕激素形式II多态,表现出比形式I更高的水溶性.
- 添加HPMCAS暂时启用了超和,并防止了在加热过程中Form II的多态转化.
- 使用HPMCAS的优化配方 (50:50乙:水) 显示出有前途的肺沉积 (MMAD 5μm),膜沉积增加,气溶性能改善 (ED 81.7%,FPF 44.5%,FPD 7.3 mg).
结论:
- 喷雾干燥是一种有效的方法,用于生产具有增强溶解性的可吸入孕激素粉末.
- HPMCAS是一种适合稳定孕激素的形式II多态的辅助剂,增加溶解度,改善吸入性质.
- 这些发现表明吸入性孕激素配方可能有更广泛的应用.
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