不同弱小有机酸对克洛法胺在水性介质中的溶解度的影响
Igor A Topalović1, Olivera S Marković2, Miloš P Pešić1
1University of Belgrade-Faculty of Chemistry, Studentski trg 12-16, 11000 Belgrade, Serbia.
Pharmaceutics
|January 8, 2025
概括
使用谷氨酸显著增加了克洛法津 (CFZ) 的溶解度,从而实现了超溶解. 这一发现有助于开发快速溶解的CFZ剂型.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 物理化学 物理化学
背景情况:
- 克洛法齐明 (CFZ) 是生物制药分类系统 (BCS) II药物,具有非常低的水溶性 (<0.01μg/mL).
- 低溶解度和吸收率导致CFZ退出美国市场.
- 100-200毫克的口服剂量需要增强溶解才能有效的口服.
研究的目的:
- 通过使用弱有机酸来研究克洛法胺 (CFZ) 的超溶解.
- 确定有机酸是否可以增强CFZ的水溶性.
- 探索开发改进CFZ配方的潜力.
主要方法:
- 测量了CFZ的水溶性作为七种弱有机酸度的函数.
- 在25°C下24小时内平衡CFZ与酸,酸和谷氨酸的5M溶液.
- 使用差分扫描热量计 (DSC) 描述形成的固体.
主要成果:
- 溶解度在5M酸,酸和谷氨酸中分别增加到0.32,1.23和10.68 mg/mL.
- 与大多数酸形成的盐或共晶体,以高点在CFZ点附近表示.
- 谷氨酸形成了添加物,在低温度 (77°C) 下转化为无形状态.
结论:
- 通过使用5M谷氨酸,CFZ的超溶解度达到10mg/ml以上.
- 谷氨酸添加物转化为无形状态提高了CFZ的溶解度.
- 这些发现支持开发快速溶解的克洛法胺剂型.
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