了解喷雾干燥无形固体分散物的辅助剂诱导的结晶
Dongyue Yu1, Meng Li2, Stephen W Hoag3
1Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, United States; Center for Materials Science and Engineering, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, United States.
药片中无形化合物-X (SDI-X) 的辅助剂诱导结晶更好地通过直接接触方法预测,如二元紧物. 这揭示了传统粉末混合物低估的结晶风险,强调辅助剂类型和接触,而不仅仅是水分.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 固态化学 固态化学
背景情况:
- 无形固体分散 (ASD) 对于提高药物的溶解性和生物可用性至关重要.
- 辅助剂诱导的结晶是影响药片配方中ASD稳定性和有效性的重大挑战.
- 准确预测药物辅助剂相互作用对于成功的药物开发至关重要.
研究的目的:
- 开发一种实用的选方法,用于评估在药片配方中的无形化合物-X (SDI-X) 的辅助剂诱导结晶.
- 为了比较不同的方法在评估SDI-X再结晶的有效性.
- 阐明助剂特性和物理接触对SDI-X结晶的影响.
主要方法:
- 使用了三种方法:二元粉末混合物,二元紧剂和双层片.
- 质量和数量评估了在加速储存条件下使用各种辅助剂进行SDI-X再结晶.
- 专注于SDI-X和辅助剂之间的物理接近和接触.
主要成果:
- 二元密集剂准确地反映了药物辅助剂在片中的接触,在预测结晶风险方面表现优于传统的二元混合物.
- 证实结晶开始于SDI-X和辅助剂之间的接触表面,如双层片所示.
- 像曼尼托尔和乳糖这样的低湿度辅料诱导了显著的结晶,表明辅料类型和接触比含水量更为关键.
结论:
- 直接物理接触方法,如二元紧物,对于评估SDI-X的辅助剂诱导结晶风险是优越的.
- 辅助剂类型和药物辅助剂接口的性质在诱导再结晶方面发挥的作用比单独的湿度显微性更为重要.
- 仔细考虑研究设计,样本准备和辅助剂选择对于可靠的药物辅助剂兼容性评估至关重要.
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