EXPANDED SOLUBILITY PARAMETER APPROACH .1. NAPHTHALENE AND BENZOIC-ACID IN INDIVIDUAL SOLVENTS

An expanded solubility parameter system was tested in conjunction with the extended Hansen solubility approach and the UNIFAC [universal functional group activity coefficient] method to calculate the solubilites of naphthalene [a model drug] and benozic acid in polar and nonpolar solvents. The expanded parameter system was characterized by .delta.d for the disperson force, .delta.p for dipolar forces, a basic or electron-donor parameter, .delta.b, and an acidic or electron-acceptor parameter .delta.a. The correlation between the calculated and observed solubilities of benzoic acid was increased by use of the 4 parameter system. An indicator variable was required to bring the solubilities into line in strongly dipolar solvents such as N,N-dimethylformamide. For naphthalene, use of the 4-parameter approach proved not to be an improvement over the 3-parameter extended Hansen solubility approach. The UNIFAC method was not successful in calculating solubilities of benzoic acid in the 40 polar and nonpolar solvents. A triangular plot of the 3 Hansen parameter for benzoic acid, p-hydroxybenzoic acid and methyl p-hydroxybenzoate illustrated the contributions of dispersion, dipolar and Lewis acid-base (H bonding) interaction forces among the 3 benzoic acid compounds and the various classes of solvents. A multiple regression procedure for calculating the 4 partial solubility parameters of drug solutes was developed.