Scholarlink

<p>Amorphous solid dispersions (ASDs) have been shown to be an effective formulation strategy for improving apparent solubility, dissolution rate, and hence oral bioavailability of poorly aqueous soluble drugs. In this perspective, we review recent progress in understanding the role of polymer concentration, particularly the overlap concentration, <i>c</i>*, in governing crystallization of high drug loaded ASDs. The overlap concentration, <i>c</i>*, is a threshold above which adjacent polymer coils start to contact. Recent work has shown that when polymer concentration is below <i>c</i>*, the presence of the continuous polymer-free amorphous drug domain allows crystallization to proceed similarly to neat drug, resulting in limited inhibition. Above <i>c</i>*, formation of a homogeneous polymer rich matrix suppresses crystallization, primarily by delaying the first nucleation event. Representative case studies demonstrate the generality of this framework across diverse drug-polymer systems, although limitations arise for sufficiently high molecular weight polymers. Overall, the <i>c</i>*-guided rheological approach provides a mechanistic basis for rational polymer selection and optimization in high drug loaded, and therefore reduced overall volume, ASD formulations.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Crystallization Inhibition and Solid-State Stability in High Drug Loaded Amorphous Drug-Polymer Dispersions Above the Overlap Concentration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月3日

查看全文
  • Sichen Song,
  • Ronald A. Siegel

摘要

Amorphous solid dispersions (ASDs) have been shown to be an effective formulation strategy for improving apparent solubility, dissolution rate, and hence oral bioavailability of poorly aqueous soluble drugs. In this perspective, we review recent progress in understanding the role of polymer concentration, particularly the overlap concentration, c*, in governing crystallization of high drug loaded ASDs. The overlap concentration, c*, is a threshold above which adjacent polymer coils start to contact. Recent work has shown that when polymer concentration is below c*, the presence of the continuous polymer-free amorphous drug domain allows crystallization to proceed similarly to neat drug, resulting in limited inhibition. Above c*, formation of a homogeneous polymer rich matrix suppresses crystallization, primarily by delaying the first nucleation event. Representative case studies demonstrate the generality of this framework across diverse drug-polymer systems, although limitations arise for sufficiently high molecular weight polymers. Overall, the c*-guided rheological approach provides a mechanistic basis for rational polymer selection and optimization in high drug loaded, and therefore reduced overall volume, ASD formulations.

Graphical Abstract