Theoretical prediction of a phase diagram for solid dispersions.

To predict the temperature-composition phase diagram of solid dispersions (SDs) through theoretical approaches using cinnarizine-Soluplus(®) SD as a model system and evaluate the predicted results. A complete phase diagram of cinnarizine-Soluplus(®) SD, including the solubility curve, miscibility curve and glass transition temperature curve, was constructed on the basis of the solid-liquid equilibrium (SLE) equation, Florry-Huggins (F-H) theory and Fox equation. Cinnarizine-Soluplus(®) SDs with different drug loadings were prepared by hot melt extrusion. The extrudates and corresponding physical mixtures were analyzed to check the predicted results. The experimental data revealed a solubility of 7.9 wt% at 110°C and a miscibility level of 65 wt% at room temperature, which were both consistent with predicted values. The predicted phase diagram agrees well with the experimental results for the non-polar components which mainly interact through dispersion forces, thus facilitating the formulation design of SDs.