Partial-solubility parameters of naproxen and sodium diclofenac

The expanded Hansen method was tested for determination of the solubility p arameters of two non-steroidal anti-inflammatory drugs, naproxen and sodium diclofenac. This work describes for the first time the application of the method to the sodium salt of a drug. The original dependent variable of the expanded Hansen method, involving the activity coefficient of the drug, wa s compared with the direct use of the logarithm of the mole fraction solubi lity lnX(2) in the solubility models. The solubility of both drugs was measured in pure solvents of several chemi cal classes and the activity coefficient was obtained from the molar heat a nd the temperature of fusion. Differential scanning calorimetry was perform ed on the original powder and on the solid phase after equilibration with t he pure solvents, enabling detection of possible changes of the thermal pro perties of the solid phase that might change the value of the activity coef ficient. The molar heal and temperature of fusion of sodium diclofenac coul d not be determined because this drug decomposed near the fusion temperatur e. The best results for both drugs were obtained with the dependent variabl e lnX(2) in association with the four-parameter model which includes the ac idic and basic partial-solubility parameters delta(a) and delta(b) instead of the Hansen hydrogen bonding parameter delta(h) Because the dispersion pa rameter does not vary greatly from one drug to another, the variation of so lubility among solvents is largely a result of the dipolar and hydrogen-bon ding parameters, a fact that is being consistently found for other drugs of small molecular weight. These results support earlier findings with citric acid and paracetamol tha t the expanded Hansen approach is suitable for determining partial-solubili ty parameters. The modification introduced in the expanded Hansen method, i .e. the use of lnX(2) as the dependent variable, provides better results th an the activity coefficient used in the original method. This is advantageo us for drugs such as sodium diclofenac for which the ideal solubility canno t be estimated. This paper shows for the first time that the method is suit able for determination of the partial-solubility parameters of a sodium sal t of a drug, sodium diclofenac.