Partial-solubility Parameters of Naproxen and Sodium Diclofenac

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Abstract
The expanded Hansen method was tested for determination of the solubility parameters 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, was compared with the direct use of the logarithm of the mole fraction solubility lnX2 in the solubility models. The solubility of both drugs was measured in pure solvents of several chemical classes and the activity coefficient was obtained from the molar heat and the temperature of fusion. Differential scanning calorimetry was performed on the original powder and on the solid phase after equilibration with the pure solvents, enabling detection of possible changes of the thermal properties of the solid phase that might change the value of the activity coefficient. The molar heat and temperature of fusion of sodium diclofenac could not be determined because this drug decomposed near the fusion temperature. The best results for both drugs were obtained with the dependent variable lnX2 in association with the four‐parameter model which includes the acidic and basic partial‐solubility parameters δa and δb instead of the Hansen hydrogen bonding parameter δh. Because the dispersion parameter does not vary greatly from one drug to another, the variation of solubility among solvents is largely a result of the dipolar and hydrogen‐bonding 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 that the expanded Hansen approach is suitable for determining partial‐solubility parameters. The modification introduced in the expanded Hansen method, i.e. the use of lnX2 as the dependent variable, provides better results than the activity coefficient used in the original method. This is advantageous for drugs such as sodium diclofenac for which the ideal solubility cannot be estimated. This paper shows for the first time that the method is suitable for determination of the partial‐solubility parameters of a sodium salt of a drug, sodium diclofenac.

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