DIFFERENTIAL MOLAR HEAT-CAPACITIES TO TEST IDEAL SOLUBILITY ESTIMATIONS

Purpose. Calculation of the ideal solubility of a crystalline solute i n a liquid solvent requires knowledge of the difference in the molar h eat capacity at constant pressure of-the sold and the supercooled liqu id forms of the solute, Delta (C) over bar(P). Since this parameter is not usually known, two assumptions have been used to simplify the exp ression. The first is that Delta (C) over bar(P) can be considered equ al to zero; the alternate assumption is that the molar entropy of fusi on, Delta (S) over bar(f) is an estimate of Delta (C) over bar(P). Rep orts 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 compoun ds of pharmaceutical interest, with melting points in the range 420 to 470K, was evaluated in this study. Methods. Solid and liquid heat cap acities of each compound near its melting point were determined using differential scanning calorimetry. Linear equations describing the hea t capacities were extrapolated to the melting point to generate the di fferential molar heat capacity. Results. Linear data were obtained for both crystal and liquid heat capacities of sample and test compounds. For each sample, ideal solubility at 298K was calculated and compared to the two estimates generated using literature equations based on th e differential molar heat capacity assumptions. Conclusions. For the c ompounds studied, Delta (C) over bar(P) was not negligible and was clo ser to Delta (S) over bar(f) than to zero. However, neither of the two assumptions was valid for accurately estimating the ideal solubility as given by the full equation.