Prevention of molecular self-association by sodium salicylate: effect on methylene blue

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(-5) M to 2 X 10(-3) M, the lambda max peak shifts from the longer wavelength region (approximately 660 nm) of the monomer toward the shorter (approximately 600 nm) indicating the presence of dimers and other oligomers. Addition of increased concentrations of sodium salicylate had a deaggregative effect on a 10(-3) M methylene blue solution, shifting the peaks toward the monomer region. On the other hand, the addition of 0.5 M 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 lambda max peak at 660 nm and generating a spectrum with one peak at approximately 600 nm, which indicated a high degree of self-association. The sodium salicylate effect is concentration dependent, with a high excess (approximately 450 times on a molar scale) being necessary to reduce the self-association. At lower concentrations of salicylate, precipitation occurs in the system.(ABSTRACT TRUNCATED AT 250 WORDS)