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药物-聚合物混合性和重叠度 (C*) 通过风湿学测量:聚合物结构的变化
Anasuya Sahoo1, Ronald A Siegel2,3
1Department of Pharmaceutics, 9-177 WDH, University of Minnesota, 308 Harvard Street S.E, Minneapolis, MN, 55455, USA.
Pharmaceutical research
|August 8, 2023
概括
无形固体分散 (ASD) 防止药物结晶,当聚合物度超过重叠度 (C*). 这一发现有助于设计稳定的药物配方,以提高生物可用性.
科学领域:
- 材料科学 材料科学 材料科学
- 制药科学 制药科学
- 物理化学 物理化学
背景情况:
- 无形固体分散 (ASDs) 通过在聚合物基质中分子分散它们来增强难溶药物的口服生物可用性.
- 高聚合物度传统上用于防止ASD中药物结晶.
- 最近的发现表明,重叠度 (C*) 是维持药物无形状态的关键聚合物度.
研究的目的:
- 评估不同度 (C) 和分子量 (MW) 的多种聚合物和药物配方的ASD固态稳定性.
- 测试假设药物结晶随着C/C*的增加而减少,并且在C > C*时被消除.
- 调查C*对聚合物MW和药物聚合物相互作用强度的依赖性.
主要方法:
- 用基托可纳和费洛迪平制备ASD,使用各种聚合物,如聚乙烯利 (PVP),聚烯酸及其共聚物.
- 聚合物在化物中的重叠度 (C*) 的风学测定.
- 通过测量聚变 (ΔHf) 和X射线衍射的度来评估药物结晶.
主要成果:
- 证实药物结晶的程度是聚合物度与重叠度 (C/C*) 的比率的函数.
- 当聚合物度超过重叠度 (C > C*) 时,基本上没有观察到药物结晶.
- 证明C*依赖于聚合物分子量和药物-聚合物相互作用.
结论:
- 这些发现为选择适当的聚合物以抑制ASD中药物结晶提供了指导.
- 通过气质学方法确定的重叠度 (C*) 可用于比较类似MW的聚合物的药物聚合物相互作用.
- 这项研究推动了稳定和生物可用无形固体分散物的合理设计.
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