<br>固体分散体中的多晶型现象,Crystal Growth & Design

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固体分散体中的多晶型现象
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2019-12-31 , DOI: 10.1021/acs.cgd.9b01138
Karina Sanabria Ortiz _{1,

2} , José R Hernández Espinell _{1,

2} , Desire Ortiz Torres _{1,

2} , Vilmalí Lopéz-Mejías _{1,

2} , Torsten Stelzer _{2,

3}

Affiliation

固体分散体将活性药物成分嵌入聚合物载体中以提高其溶解度。通常采用三种固体分散体制备技术：溶剂蒸发法、溶剂熔融法和熔融法。尽管这些也被广泛推荐作为相图测定的制备方法，但一旦产生固体分散体，关于它们对所得多晶型物的影响的例子很少。在本研究中，研究了这些方法对由氟芬那酸（FFA）和聚乙二醇组成的结晶固体分散体（CSD）中获得的多晶型的影响。通过粉末 X 射线衍射、红外光谱和差示扫描量热法对物理混合物和 CSD 进行了表征。结果表明，融合方法会在 CSD 中产生伴随的多晶型物（主要是 FFA I 和 III）。相反，溶剂蒸发和溶剂融合方法产生 FFA III。总的来说，这些结果表明，制备方法对确定的相图有显着影响（平均相对偏差≤8%），相图通常用于证明制造工艺的设计空间，包括那些被视为“连续”的制造工艺。因此，选择产生所需多晶型物的制备方法对于确保准确确定制剂的相图和关键质量属性至关重要。

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Polymorphism in Solid Dispersions

Solid dispersions embed active pharmaceutical ingredients in polymeric carriers to improve their solubility. Three solid dispersion preparation techniques are typically employed: solvent evaporation, solvent-fusion, and fusion methods. Although these are also widely recommended as preparative methods for phase diagram determination, few examples exist concerning their effect on the resulting polymorph, once the solid dispersion is produced. In this study, the influence of these methods on the polymorphic form obtained in crystalline solid dispersions (CSDs) composed of flufenamic acid (FFA) and polyethylene glycol was investigated. The physical mixtures and CSDs were characterized by powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry. The results reveal that the fusion method leads to concomitant polymorphs (mainly FFA I and III) in the CSDs. In contrast, the solvent evaporation and solvent-fusion methods lead to FFA III. Collectively, these results demonstrate that preparative methods have a significant influence on the phase diagrams determined (average relative deviation ≤8%), which are often used to justify the design space of manufacturing processes, including those deemed “continuous.” Consequently, choosing a preparation method that results in the desired polymorph is crucial to ensure accurate determination of phase diagrams and critical quality attributes of formulations.

更新日期：2020-01-01

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