Proposition of group molar constants for sodium to calculate the partial solubility parameters of sodium salts using the van Krevelen group contribution method

The aim of this study is to propose, for the first time, a set of group mol ar constants for sodium to calculate the partial solubility parameters of s odium salts. The values were estimated using the few experimental partial s olubility parameters of acid/sodium salt series available either from the l iterature (benzoic acid/Na, ibuprofen acid/Na, diclofenac Na) or determined in this work (salicylic acid/Na, p-aminobenzoic acid/Na, diclofenac), the group contribution method of van Krevelen to calculate the partial paramete rs of the acids, and three reasonable hypothesis. The experimental method u sed is a modification of the extended Hansen approach based on a regression analysis of the solubility mole fraction of the drug In X-2 against models including three- or four-partial solubility parameters of a series of pure solvents ranging from non-polar (heptane) to highly polar (water). The mod ified method combined with the four-parameter model provided the best resul ts for both acids and sodium derivatives. The replacement of the acidic pro ton by sodium increased the dipolar and basic partial solubility parameters , whereas the dispersion parameter remained unaltered, thus increasing the overall total solubility parameter of the salt. The proposed group molar co nstants of sodium are consistent with the experimental results as sodium ha s a relatively low London dispersion molar constant (identical to that of - OH), a very high Keesom dipolar molar constant (identical to that of -NO2, two times larger than that of -OH), and a very high hydrogen bonding molar constant (identical to that of -OH). The proposed values are: F-(Na)d = 270 (J cm(3))(1/2) mol(-1); F-(Na)d = 1030 (J cm(3))(1/2) mol(-1); U-(Na)h = 1 7 000 J mol(-1). Like the constants for the other groups, the group molar c onstants proposed for sodium are certainly not the exact values. However, t hey are believed to be a fair approximation of the impact of sodium on the partial solubility parameters and, therefore, can be used as such in the gr oup contribution method of van Krevelen. (C) 2000 Elsevier Science B.V. All rights reserved.