Neau S H, Bhandarkar S V, Hellmuth E W
School of Pharmacy, University of Missouri, Kansas City 64110-2499, USA.
Pharm Res. 1997 May;14(5):601-5. doi: 10.1023/a:1012148910975.
Calculation of the ideal solubility of a crystalline solute in a liquid solvent requires knowledge of the difference in the molar heat capacity at constant pressure of the solid and the supercooled liquid forms of the solute, delta Cp. Since this parameter is not usually known, two assumptions have been used to simplify the expression. The first is that delta Cp can be considered equal to zero; the alternate assumption is that the molar entropy of fusion, delta Sf, is an estimate of delta Cp. Reports claiming the superiority of one assumption over the other, on the basis of calculations done using experimentally determined parameters, have appeared in the literature. The validity of the assumptions in predicting the ideal solubility of five structurally unrelated compounds of pharmaceutical interest, with melting points in the range 420 to 470 K, was evaluated in this study.
Solid and liquid heat capacities of each compound near its melting point were determined using differential scanning calorimetry. Linear equations describing the heat capacities were extrapolated to the melting point to generate the differential molar heat capacity.
Linear data were obtained for both crystal and liquid heat capacities of sample and test compounds. For each sample, ideal solubility at 298 K was calculated and compared to the two estimates generated using literature equations based on the differential molar heat capacity assumptions.
For the compounds studied, delta Cp was not negligible and was closer to delta Sf than to zero. However, neither of the two assumptions was valid for accurately estimating the ideal solubility as given by the full equation.
计算结晶溶质在液体溶剂中的理想溶解度需要了解溶质的固态和过冷液态在恒压下的摩尔热容之差，即ΔCp。由于该参数通常未知，人们采用了两种假设来简化表达式。第一种假设是可以认为ΔCp等于零；另一种假设是熔化摩尔熵ΔSf是ΔCp的估计值。基于使用实验确定的参数进行的计算，文献中出现了声称一种假设优于另一种假设的报告。本研究评估了这些假设在预测熔点范围为420至470K的五种结构不相关的药用化合物的理想溶解度方面的有效性。
使用差示扫描量热法测定每种化合物在其熔点附近的固态和液态热容。将描述热容的线性方程外推至熔点以生成微分摩尔热容。
获得了样品和测试化合物的晶体和液体热容的线性数据。对于每个样品，计算了298K时的理想溶解度，并与基于微分摩尔热容假设使用文献方程生成的两个估计值进行了比较。
对于所研究的化合物，ΔCp不可忽略，且更接近ΔSf而非零。然而，这两种假设都不能有效地准确估计完整方程给出的理想溶解度。
