Dissolution Capacity Of Hydrophobic Drugs In Aqueous Solution--Solubility And Diffusion Gibbs Free Energy

The Solubility and diffusion coefficient of drugs in aqueous solution are essential physicochemical parameters which affect the bioavailability of drugs.In this paper, we have measured the solubility of silymarin, a Chinese traditional medicine drug effective ingredient, in aqueous solutions of some polymers, (Polyethylene glycol 6000 , Polyvinylpyrrolidone k30, Dextran 40000). The effect of sucrose on the diffusion property for heptanedioic acid, a hydrophobic model molecule, dissolved in aqueous solution has been studied.1. Solubilities of silymarin in water have been measured by using a solid-liquid equilibrium cell within the temperature range from 293.15 to 313.15 K. An equation of solubility has been obtained on the base of solid-liquid equilibrium theory. The experimental data have been correlated by using this equation and other empirical equations. Some thermodynamic properties, such as solution enthalpy, have been calculated. The factors which affect the solubilities of silymarin in water have been discussed.2. Solubilities of silymarin in aqueous solutions of PEG 6000, PVPk30, Dex 40000 have been measured by using a solid-liquid equilibrium cell within the temperature range from 293.15 to 313.15 K. A correlation equation of solubility has been proposed by using Kirkwood-Buff s solution theory and the Flory-Huggins activity coefficient equations. The results of correlation indicate that the mean relative errors are 2.2% and 4.3% for systems of water + PEG 6000 and water + PVP k30, respectively. The enthalpy and entropy changes of the systems of water + PEG 6000 and PVP k30 have been discussed on the base of enthalpy-entropy compensation, which reveals the dissolution mechanism of silymarin in aqueous polymer solution. The dissolution enthalpies of silymarin in aqueous solutions of PEG 6000 and PVP k30 decrease gradually with the increase in polymers concentration, which indicates the dissolution of silymarin is driven by enthalpy. The effects of polarity of medium on the solubility of silymarin in aqueous solution have beendiscussed.3. Data of viscosity and density for the system of heptanedioic acid dissolved in aqueous sucrose solution at temperature range from 288.15 to 313.15 K have been measured. On the basis of the Feakins equation, the activation parameters (△u3≠, △H3≠, △S3≠, △G120≠, △H120≠ and △S120≠) for viscous flow of the solution have been evaluated, together with the Gibbs energy of transfer for the solute from the ground state solvent to the hypothetical viscous transition state solvent, △G3≠(1-1'). The physical meaning of △G3≠(1-1') is the diffusion Gibbs free energy of solute 3 in solvents 1 and 1'. The effect of temperature and sucrose's concentration on these parameters has been discussed. The results indicate that the values of △u3≠ decrease with an increase in temperature, but the values of △H3≠, △S2≠ and the diffusion Gibbs energy of solute increase with the increase in sucrose concentration. This means that the diffusion of heptanedioic acid in water becomes more difficult with the addition of sucrose into the solution.