SOLUBILITY ENHANCEMENT OF NUCLEOSIDES AND STRUCTURALLY RELATED-COMPOUNDS BY COMPLEX-FORMATION

Water-soluble vitamins, amino acids, and nontoxic pharmaceutical excip ients were studied as solubilizing agents for poorly water-soluble ade nine (nucleic acid base), guanosine (nucleoside), and structurally rel ated drugs (acyclovir and triamterene). The apparent solubility of the substrates (adenine, guanosine, acyclovir, or triamterene) was apprec iably increased by forming complexes with the ligands (vitamins, amino acids, or other ligand). Apparent association constants (K-a) values were measured at 25 degrees C in pH 7 phosphate buffer using phase sol ubility analysis. The effect of combination ligands on substrate solub ility was also studied. Additive solubility enhancement was obtained f or several ligand pairs.