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 ap plication. The solvents tested were (I): dibutyl adipate, di(2-ethylhe xyl) 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 polari ty. Naproxen was also tested in the mixtures (II) of these solvents wi th others of higher polarity (ethyl and isopropyl alcohol) in proporti ons such that, according to the theory, the parameter of the mixture e quals that of the solute. It was found that, despite the low polarity of the initial solvents (I), naproxen only seems to form regular solut ions with some of them (di(2-ethylhexyl) adipate, 2-octyldodecanol and oleyl alcohol), whereas in the others both negative and positive devi ations were observed as regards the solubility values predicted by the theory. These deviations may be due to the chameleonic characteristic s of the solute, inducing different solute-solute or solute-solvent in teractions, depending on the polarity of the solvent. This may also ex plain the diverse, substantial increases in solubility of naproxen in the different mixtures (II).