...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Fluid Phase Equilibria >An evaluation of thermodynamic models for the prediction of drug and drug-like molecule solubility in organic solvents
【24h】

An evaluation of thermodynamic models for the prediction of drug and drug-like molecule solubility in organic solvents

机译：用于预测药物和类药物分子在有机溶剂中溶解度的热力学模型的评估

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Prediction of solubility of active pharmaceutical ingredients (API) in different solvents is one of the main issue for crystallization process design. Experimental determination is not always possible because of the small amount of product available in the early stages of a drug development. Thus, one interesting perspective is the use of thermodynamic models, which are usually employed for predicting the activity coefficients in case of Vapour-Liquid equilibria or Liquid-Liquid equilibria (VLE or LLE). The choice of the best thermodynamic model for Solid-Liquid equilibria (SLE) is not an easy task as most of them are not meant particularly for this. In this paper, several models are tested for the solubility prediction of five drugs or drug-like molecules: Ibuprofen, Acetaminophen, Benzoic acid, Salicylic acid and 4-aminobenzoic acid, and another molecule, anthracene, a rather simple molecule. The performance of predictive (UNIFAC, UNIFAC mod., COSMO-SAC) and semi-predictive (NRTL-SAC) models are compared and discussed according to the functional groups of the molecules and the selected solvents. Moreover, the model errors caused by solid state property uncertainties are taken into account. These errors are indeed not negligible when accurate quantitative predictions want to be performed. It was found that UNIFAC models give the best results and could be an useful method for rapid solubility estimations of an API in various solvents. This model achieves the order of magnitude of the experimental solubility and can predict in which solvents the drug will be very soluble, soluble or not soluble. In addition, predictions obtained with NRTL-SAC model are also in good agreement with the experiments, but in that case the relevance of the results is strongly dependent on the model parameters regressed from solubility data in single and mixed solvents. However, this is a very interesting model for quick estimations like UNIFAC models. Finally, COSMO-SAC needs more developments to increase its accuracy especially when hydrogen bonding is involved. In that case, the predicted solubility is always overestimated from two to three orders of magnitude. Considering the use of the most accurate equilibrium equation involving the ΔC_p term, no benefits were found for drug predictions as the models are still too inaccurate. However, in function of the molecules and their solid thermodynamic properties, the ΔC_p term can be neglected and will not have a great impact on the results.
机译：预测活性药物成分（API）在不同溶剂中的溶解度是结晶工艺设计的主要问题之一。由于在药物开发的早期可获得的产品量很少，因此实验确定并非总是可行的。因此，一种有趣的观点是热力学模型的使用，在蒸汽-液体平衡或液体-液体平衡（VLE或LLE）的情况下，通常使用该模型来预测活度系数。为固液平衡（SLE）选择最佳的热力学模型并不是一件容易的事，因为其中大多数并不是专门为此目的而设计的。在本文中，测试了几种模型以预测五种药物或类药物分子的溶解度：布洛芬，对乙酰氨基酚，苯甲酸，水杨酸和4-氨基苯甲酸，以及另一个分子蒽（一个相当简单的分子）。根据分子的官能团和所选溶剂，比较和讨论了预测模型（UNIFAC，UNIFAC mod。，COSMO-SAC）和半预测模型（NRTL-SAC）的性能。此外，考虑了由固态性质不确定性引起的模型误差。当要执行准确的定量预测时，这些误差确实不可忽略。已发现UNIFAC模型可提供最佳结果，并且可能是快速估算API在各种溶剂中的溶解度的有用方法。该模型达到了实验溶解度的数量级，并可以预测药物在哪种溶剂中非常易溶，可溶或不可溶。另外，使用NRTL-SAC模型获得的预测也与实验非常吻合，但是在这种情况下，结果的相关性很大程度上取决于从单一和混合溶剂中的溶解度数据得出的模型参数。但是，对于UNIFAC模型这样的快速估算而言，这是一个非常有趣的模型。最后，COSMO-SAC需要进一步发展以提高其准确性，尤其是在涉及氢键的情况下。在这种情况下，预测的溶解度总是被高估了两个到三个数量级。考虑到使用涉及ΔC_p项的最准确的平衡方程，由于模型仍然不太准确，因此未发现药物预测的益处。但是，就分子的功能及其固体热力学性质而言，ΔC_p项可以忽略，不会对结果产生很大影响。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号