Hydrotropic Solubilization of Sparingly Soluble Riboflavin Drug Molecule in Aqueous Nicotinamide Solution

We study the effect of hydrotrope nicotinamide on the solubilization of sparingly soluble riboflavin drug molecule. Nicotinamide molecules self-associate through stacking of their pyridine rings, and they also form complexes with riboflavin molecules. Water molecules only prefer to stay at the periphery of the riboflavin molecules, and they are replaced by the hydrotrope molecules with increasing concentration of the solution. The analyses of orientation distributions and distance measurements reveal that the riboflavin and nicotinamide molecules form 1:2 sandwich complexes. It is demonstrated that the self-aggregation of nicotinamide and the complexation between riboflavin and nicotinamide does not have much influence on the number of water-water average hydrogen bonds but they influence the riboflavin-water, nicotinamide-water, riboflavin-riboflavin, riboflavin-nicotinamide, and nicotinamide-nicotinamide hydrogen bonds. Favorable van der Waals interaction energy between riboflavin and nicotinamide plays an important role in the 1:1 or 1:2 complex formation between drug and hydrotrope molecules. The electrostatic energy component of drug and hydrotrope interaction also contributes to the solubilization process. The negative Flory-Huggins interaction parameter value suggests the favorable interactions between the hydrotrope and drug molecules.