AN APPLICATION OF REGULAR SOLUTION THEORY IN THE STUDY OF THE SOLUBILITY OF NAPROXEN IN SOME SOLVENTS USED IN TOPICAL PREPARATIONS

The solubility of naproxen was studied in different solvents in order to test the possible application of the theory of regular solutions in preformulation studies of a pharmaceutical form for dermatological application. The solvents tested were (I): dibutyl adipate, di(2-ethylhexyl) adipate, oleyl alcohol, propylene glycol dipelargonate, isopropyl myristate, 2-octyldodecanol, decyl oleate, oleyl oleate and isopropyl palmitate. These solvents are normally used in the production of this type of pharmaceutical form and are characterised by their low polarity. Naproxen was also tested in the mixtures (II) of these solvents with others of higher polarity (ethyl and isopropyl alcohol) in proportions such that, according to the theory, the parameter of the mixture equals that of the solute. It was found that, despite the low polarity of the initial solvents (I), naproxen only seems to form regular solutions with some of them (di(2-ethylhexyl) adipate, 2-octyldodecanol and oleyl alcohol), whereas in the others both negative and positive deviations were observed as regards the solubility values predicted by the theory. These deviations may be due to the chameleonic characteristics of the solute, inducing different solute-solute or solute-solvent interactions, depending on the polarity of the solvent. This may also explain the diverse, substantial increases in solubility of naproxen in the different mixtures (II).