The modified extended Hansen method to determine partial solubility parameters of drugs containing a single hydrogen bonding group and their sodium derivatives: benzoic acid/Na and ibuprofen/Na

Sodium salts are often used in drug formulation but their partial solubilit y parameters are not available. Sodium alters the physical properties of th e drug and the knowledge of these parameters would help to predict adhesion properties that cannot be estimated using the solubility parameters of the parent acid. This work tests the applicability of the modified extended Ha nsen method to determine partial solubility parameters of sodium salts of a cidic drugs containing a single hydrogen bonding group (ibuprofen, sodium i buprofen. benzoic acid and sodium benzoate). The method uses a regression a nalysis of the logarithm of the experimental mole fraction solubility of th e drug against the partial solubility parameters of the solvents, using mod els with three and four parameters. The solubility of the drugs was determi ned in a set of solvents representative of several chemical classes, rangin g from low to high solubility parameter values. The best results were obtai ned with the four parameter model for the acidic drugs and with the three p arameter model for the sodium derivatives. The four parameter model include s both a Lewis-acid and a Lewis-base term, Since the Lewis acid properties of the sodium derivatives are blocked by sodium, the three parameter model is recommended for these kind of compounds, Comparison of the parameters ob tained shows that sodium greatly changes the polar parameters whereas the d ispersion parameter is not much affected. Consequently the total solubility parameters of the salts are larger than for the parent acids in good agree ment with the larger hydrophilicity expected from the introduction of sodiu m. The results indicate that the modified extended Hansen method can br: ap plied to determine the: partial solubility parameters of acidic drugs and t heir sodium salts. (C) 2000 Elsevier Science B.V. All rights reserved.