Amorphous solid dispersion (SD) technique has been used for improving the solubility and bioavailability of poorly water-soluble compounds. However, the stability of these SD is a concern due to the high propensity of metastable amorphous form to convert into its stable crystalline form. In this study, the stability of SD of griseofulvin (GSV), a high crystallization tendency compound, was evaluated in the presence of commonly used Food and Drug Administration-approved hydrophilic polymers such as polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose, Eudragits, and polyethylene glycol. Physical mixtures (PM) and SD were prepared at various drug to polymer ratios (3:1, 1:1, 1:2, 1:9 w/w) using the solvent evaporation technique. PM and SD were characterized by powder X-ray diffractometer and modulated differential scanning calorimetry to confirm the formation of amorphous dispersions and to understand the crystallization inhibition effectiveness of polymers. Infrared (IR), Raman spectroscopy, and molecular modeling were used to understand the role of interaction between GSV and polymers for stabilization of dispersions. We observed that most polymers are ineffective in stabilizing the amorphous form of GSV at low concentrations, that is, 3:1, 1:1, and 1:2 w/w except for PVP K-90, which was effective at a concentration of 1:1 w/w. Slight peak shifts were observed in IR and Raman; however, these shifts were inconclusive of molecular interactions between GSV and hydrophilic polymers. GSV's high crystallization tendency coupled with a lack of hydrogen bond acceptors/donors hinders the formation of stable SD, and thus, a higher polymer concentration is a prerequisite for their long-term stability.

中文翻译：

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灰黄霉素固体分散体的制备和表征。

非晶态固体分散体（SD）技术已用于改善水溶性差的化合物的溶解度和生物利用度。然而，由于亚稳态无定形形式转变成其稳定的结晶形式的可能性很高，因此这些SD的稳定性令人担忧。在这项研究中，灰黄霉素（GSV）（一种高结晶趋势化合物）的SD稳定性在食品和药物管理局批准的常用亲水性聚合物（如聚乙烯吡咯烷酮（PVP），羟丙基甲基纤维素，Eudragits和聚乙烯）的存在下进行了评估乙二醇。使用溶剂蒸发技术以各种药物与聚合物的比例（3：1、1：1、1：2、1：9 w / w）制备物理混合物（PM）和SD。通过粉末X射线衍射仪和调制差示扫描量热法对PM和SD进行了表征，以确认无定形分散体的形成并了解聚合物的结晶抑制效果。红外（IR），拉曼光谱和分子模型被用来了解GSV和聚合物之间的相互作用对于稳定分散体的作用。我们观察到，大多数聚合物在低浓度（即3：1、1、1：1和1：2 w / w）下无法稳定GSV的无定形形式，但PVP K-90的浓度为50％时有效。 1：1 w / w。在IR和拉曼中观察到轻微的峰移动；然而，这些变化并不意味着GSV和亲水性聚合物之间的分子相互作用。GSV'