Solubility enhancement of nucleosides and structurally related compounds by complex formation.

Water-soluble vitamins, amino acids, and nontoxic pharmaceutical excipients were studied as solubilizing agents for poorly water-soluble adenine (nucleic acid base), guanosine (nucleoside), and structurally related drugs (acyclovir and triamterene). The apparent solubility of the substrates (adenine, guanosine, acyclovir, or triamterene) was appreciably increased by forming complexes with the ligands (vitamins, amino acids, or other ligand). Apparent association constants (Ka) values were measured at 25 degrees C in pH 7 phosphate buffer using phase solubility analysis. The effect of combination ligands on substrate solubility was also studied. Additive solubility enhancement was obtained for several ligand pairs.