Ochsner A B, Sokoloski T D
J Pharm Sci. 1985 Jun;74(6):634-7. doi: 10.1002/jps.2600740610.
There is a need to identify suitable blends of solvents to dissolve drugs. Empirical approaches, such as trial-and-error and response surface, require several solubility measurements. In this study the UNIFAC method was used to predict solubility in highly nonideal multicomponent systems in which only the solute enthalpy of fusion and melting point must by measured. UNIFAC combines a group contribution approach with the UNIQUAC model for activity coefficients. Parameters characterizing interactions among constituent groups of a molecule have been previously determined from binary vapor pressure data. These tabulated group parameters are used to predict activity coefficients for newly synthesized compounds. These coefficients, together with the ideal solubility, permit a prediction of solubility. The solubility of 4-hexylresorcinol in ethyl acetate, ethyl myristate, and hexane mixtures was both measured and calculated using UNIFAC. The predicted solubilities were within 10% of the experimental solubilities for all but 3 of 21 mixtures. Since the method accounted for positive and negative deviations from ideality in a hydrogen-bonding system of molecules having different sizes, it shows great potential for use in pharmacy.
需要确定合适的溶剂混合物来溶解药物。经验方法，如试错法和响应面法，需要进行多次溶解度测量。在本研究中，使用UNIFAC方法预测在高度非理想多组分体系中的溶解度，在该体系中仅需测量溶质的熔化焓和熔点。UNIFAC将基团贡献法与用于活度系数的UNIQUAC模型相结合。表征分子组成基团间相互作用的参数先前已从二元蒸气压数据中确定。这些列表化的基团参数用于预测新合成化合物的活度系数。这些系数与理想溶解度一起，可用于预测溶解度。使用UNIFAC测量并计算了4-己基间苯二酚在乙酸乙酯、肉豆蔻酸乙酯和己烷混合物中的溶解度。对于21种混合物中的21种混合物，除了3种混合物外，预测溶解度与实验溶解度的偏差在10%以内。由于该方法考虑了具有不同尺寸的分子的氢键体系中与理想情况的正偏差和负偏差，因此在药学领域显示出巨大的应用潜力。
