Self-association of analgesics in aqueous solution: association models for codeine, oxycodone, ethylmorphine and pethidine.

Light scattering, vapour pressure osmometry, conductivity and surface tension techniques have been used to examine aqueous solutions of several narcotic analgesics for evidence of association. Contrary to a previous report, no significant association could be detected in solutions of morphine sulphate and codeine phosphate. Other drugs which showed no evidence of aggregation in water included morphine hydrochloride, ethylmorphine hydrochloride, oxycodone hydrochloride and dihydrocodeine tartrate. Self-association of ethylmorphine hydrochloride, oxycodone hydrochloride and codeine phosphate was observed in the presence of 0.5 mol dm-3 electrolyte, the pattern of association conforming to that of a stepwise association process with all association constants of equal value. The association of pethidine hydrochloride in 0.5 mol dm-3 sodium chloride could be represented by an association scheme in which association constant KN increased sequentially with aggregation number N according to the relation KN = K(N - 1)/N.