A mechanistic study of hydrotropic solubilization: Riboflavin -nicotinamide in aqueous and non-aqueous systems
Solubilization of riboflavin by nicotinamide, a hydrotropic agent, in both aqueous and non-aqueous systems was investigated. The solubility of riboflavin in all solvent systems was increased by adding various concentrations of nicotinamide. The ability of nicotinamide to solubilize riboflavin in solution at a constant temperature was greatest in water and decreased in the following order: methanol > ethanol > n-propanol > isopropanol. As the temperature was increased, the solubility of riboflavin in nicotinamide solution increased. Heat of solution of riboflavin in each solvent system accounted for the variation in the rate of increase of riboflavin solubility with temperature changes and thus a solvent effect was hypothesized for this behavior. Enthalpy of riboflavin solution was obtained from van't Hoff plot. The relationship between the enthalpy of riboflavin solution and nicotinamide concentration was shown to be non-linear. To understand the molecular interaction between nicotinamide and various solvent systems the concept of enthalpy and entropy compensation was applied. Thermodynamic parameters of riboflavin solution were evaluated at the harmonic mean temperature. The relationship between the enthalpy and the entropy of a riboflavin solution was linear. It was found that there was a functional relationship between the free energy and the enthalpy of riboflavin solution supporting the conclusion that solvent compensation occurred. In an aqueous system of nicotinamide at concentrations lower than 0.01 molar, enthalpy and entropy transfer increased, suggesting that the strength of the hydrogen bond within the water structure was enhanced by the presence of nicotinamide and riboflavin solubility was entropy driven. At higher concentrations (>0.01 M), the formation of a more ordered solvent structure was proposed in which riboflavin was enthalpy driven. A similar phenomenon was observed in nicotinamide-methanol solution. A mechanism identical to that of nicotinamide-water system was proposed for nicotinamide-methanol solution based on similarities in the structure of water and methanol. In ethanol, n-propanol and isopropanol, no initial increase in enthalpy and entropy was observed. The effect of inserting a nicotinamide molecule within the chain-like structure of these three aliphatic alcohols resulted in a more ordered structure and solubility was enthalpy driven. Nicotinamide acts as a cosolvent in enhancing the solubility of riboflavin. ^
Major Professor: Dane O. Kildsig, Purdue University.
Health Sciences, Pharmacy