Hansen solubility parameter as a tool to predict cocrystal formation
Hansen solubility parameter as a tool to predict cocrystal formation
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DOI：
10.1016/j.ijpharm.2011.01.030
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发表时间：
2011-04-04
影响因子：
5.8
通讯作者：
Velaga, Sitaram P.
中科院分区：
文献类型：
--
作者：
Mohammad, Mohammad Amin;Alhalaweh, Amjad;Velaga, Sitaram P.
本研究的目的是研究药物和共形成物的溶解度，如由汉森溶解度参数（HSP）预测的，是否可以指示共晶形成并指导共晶筛选。这也是我们的目标，以评估各种HSP为基础的方法在可预测性。根据基团贡献法计算了吲哚美辛（模型药物）和三十多种共形成物的热休克蛋白。然后使用三种已建立的方法计算吲哚美辛和每种共形成物之间的HSP差异，并预测相容性。随后，差示扫描量热法被用来研究实验的可溶解性和共晶形成。还使用液体辅助研磨验证了共晶的形成。除一种药物共形成物外，所有被预测为可混溶的药物共形成物均被实验证实为可混溶的。所有测试的理论方法都在预测兼容性的协议。所有形成共晶的体系都是可混溶的。值得注意的是，在这项研究中发现了两种新的吲哚美辛共晶。虽然可能有必要在广泛的不同共形成物和药物化合物类型中测试这种方法以进行准确的概括，但测试系统的趋势是明确的，并表明药物和共形成物应该是可混溶的以形成共晶体。因此，使用溶解度参数预测共晶组分的溶解度可以在详尽的共晶筛选工作之前指导潜在共形成物的选择。(C)2011 Elsevier B.V.保留所有权利。
The objective of this study was to investigate whether the miscibility of a drug and coformer, as predicted by Hansen solubility parameters (HSPs), can indicate cocrystal formation and guide cocrystal screening. It was also our aim to evaluate various HSPs-based approaches in miscibility prediction. HSPs for indomethacin (the model drug) and over thirty coformers were calculated according to the group contribution method. Differences in the HSPs between indomethacin and each coformer were then calculated using three established approaches, and the miscibility was predicted. Subsequently, differential scanning calorimetry was used to investigate the experimental miscibility and cocrystal formation. The formation of cocrystals was also verified using liquid-assisted grinding. All except one of the drug-coformers that were predicted to be miscible were confirmed experimentally as miscible. All tested theoretical approaches were in agreement in predicting miscibility. All systems that formed cocrystals were miscible. Remarkably, two new cocrystals of indomethacin were discovered in this study. Though it may be necessary to test this approach in a wide range of different coformer and drug compound types for accurate generalizations, the trends with tested systems were clear and suggest that the drug and coformer should be miscible for cocrystal formation. Thus, predicting the miscibility of cocrystal components using solubility parameters can guide the selection of potential coformers prior to exhaustive cocrystal screening work. (C) 2011 Elsevier B.V. All rights reserved.