title: Proposition of group molar constants for sodium to calculate the partial solubility parameters of sodium salts using the van Krevelen group contribution method.
abstract: The aim of this study is to propose, for the first time, a set of group molar constants for sodium to calculate the partial solubility parameters of sodium salts. The values were estimated using the few experimental partial solubility parameters of acid/sodium salt series available either from the literature (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 parameters of the acids, and three reasonable hypothesis. The experimental method used is a modification of the extended Hansen approach based on a regression analysis of the solubility mole fraction of the drug lnX(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 modified method combined with the four-parameter model provided the best results for both acids and sodium derivatives. The replacement of the acidic proton 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 constants of sodium are consistent with the experimental results as sodium has a relatively low London dispersion molar constant (identical to that of -OH), a very high Keesom dipolar molar constant (identical to that of -NO(2), 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)p)=1030 (J cm(3))(1/2) mol(-1); U((Na)h)=17000 J mol(-1). Like the constants for the other groups, the group molar constants proposed for sodium are certainly not the exact values. However, they 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 group contribution method of van Krevelen.
authors.affiliation: School of Pharmacy, University of Geneva, Quai Ernest-Ansermet 30, 1211, Geneva, Switzerland. jerome.barra@firmenich.com
authors.forename: J
authors.initials: J
authors.lastname: Barra
authors.forename: M A
authors.initials: MA
authors.lastname: Peña
authors.forename: P
authors.initials: P
authors.lastname: Bustamante
mesh_terms: D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012492:Salts; D012964:Sodium / Q000737:chemistry*; D012995:Solubility; D012997:Solvents
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004364:Pharmaceutical Preparations; D012492:Salts; D012997:Solvents; D012964:Sodium