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 solubility parameters are not available. Sodium alters the physical properties of the 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 Hansen method to determine partial solubility parameters of sodium salts of acidic drugs containing a single hydrogen bonding group (ibuprofen, sodium ibuprofen, benzoic acid and sodium benzoate). The method uses a regression analysis of the logarithm of the experimental mole fraction solubility of the drug against the partial solubility parameters of the solvents, using models with three and four parameters. The solubility of the drugs was determined in a set of solvents representative of several chemical classes, ranging from low to high solubility parameter values. The best results were obtained with the four parameter model for the acidic drugs and with the three parameter model for the sodium derivatives. The four parameter model includes 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 obtained shows that sodium greatly changes the polar parameters whereas the dispersion parameter is not much affected. Consequently the total solubility parameters of the salts are larger than for the parent acids in good agreement with the larger hydrophilicity expected from the introduction of sodium. The results indicate that the modified extended Hansen method can be applied to determine the partial solubility parameters of acidic drugs and their sodium salts.
Bustamante
P
P
Department of Farmacia y Tecnolog¿ia Farmac¿eutica, Facultad de Farmacia, Universidad de Alcal¿a, Alcal¿a de Henares, 28871, Madrid, Spain. tfpbm@farma.alcala.es
Pena
M A
MA
Barra
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry*; D019817:Benzoic Acid / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D012492:Salts / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D020160:Sodium Benzoate / Q000737:chemistry*; D012995:Solubility; D012997:Solvents
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000935:Antifungal Agents; D012492:Salts; D012997:Solvents; D019817:Benzoic Acid; D012964:Sodium; D020160:Sodium Benzoate; D007052:Ibuprofen