Thermodynamic Study And Modeling For Solid Dispersions Of Silybin

Solid dispersion technology can improve the dissolution rate of poorly soluble drugs. But it was restricted by many factors. In our paper, silybin was selected as the model of hydrophobic molecule. Thermodynamic properties of solid dispersions of silybin were studied in this work, and it provides the theoretical and technological basis about the application and improvement of solid dispersions. It included:1. Solid dispersions (SD) of PEG 6000 and Poloxamer 188 with silybin were prepared by fusion-cooling method, respectively. The T-wt% and Δ_fusH_w-wt% diagrams were constructed by DSC method. Experimental results indicated that the eutectic points of solid dispersions were dropped significantly. Interaction parameters of the Flory-Huggins model were correlated from experimental data. Theoretical model predicted the T-wt% and Δ_fusH_w-wt% diagram with a fairly good agreement with experiment. Silybin can be easily dispersed into the carries solution, since the molecular interaction (hydrogen bonding) favors to the mixing process.2. The relationship of T-wt% and Δ_fusH_w-wt% of SD which were prepared by mixing silybin with a binary mixed carrier, PVP k30 + PEG 6000, were studied by DSC method. Experimental result reveals that the fusion temperature and Δ_fusH_w of (PVP k30 + PEG 6000) were lower than PEG 6000. The eutectic point of the SD was also decreased.3. In order to study the molecular interaction between the drug and the carriers, IR spectroscopy and X-ray diffraction were measured. It reveals that silybin had dispersed into the carriers with microcrystalline, super microcrystalline or amorphous state, and no chemical reaction take placed between these two components.And we studied the viscosity of aqueous solution of Dextran 40000 and adipic acid in order to obtain the transport properties of the solution. Experimental results indicated that the viscosities and densities of two solutions were increased with the increasing in temperature. The viscous B-coefficient drops with the increasing in temperature.