Prevention of Molecular Self-Association by Sodium Salicylate: Effect on Methylene Blue

Abstract

Sodium salicylate improves the rectal absorption of drugs which exhibit molecular self-association; it is suggested that salicylate may improve drug bioavailability by altering the drug self-association pattern. Methylene blue was chosen as a model molecule for investigating the interference of salicylate with drugs undergoing self-association. The effect of sodium salicylate on the concentration-dependent association of methylene blue as expressed by metachromasy was observed and compared with the effects of other additives: urea, sodium chloride, sodium acetate, sodium sulfate, and sodium benzoate. By increasing the methylene blue concentration from 10−5M to 2 × 10−3M, the λmax peak shifts from the longer wavelength region (∼660nm) of the monomer toward the shorter (600nm) indicating the presence of dimers and other oligomers. Addition of increased concentrations of sodium salicylate had a deaggregative effect on a 10−3M methylene blue solution, shifting the peaks toward the monomer region. On the other hand, the addition of 0.5M of any of the following salts: sulfate, acetate, or chloride, to a 10−3 M, aqueous solution of methylene blue had the opposite effect, eliminating the λmax peak at 660nm and generating a spectrum with one peak at ∼600nm, which indicated a high degree of self-association. The sodium salicylate effect is concentration dependent, with a high excess (∼450 times on a molar scale) being necessary to reduce the self-association. At lower concentrations of salicylate, precipitation occurs in the system. The results show that although sodium salicylate and urea are both agents favoring methylene blue dissociation, the salicylate effect is much more potent and appears to be mechanistically different.