Solid dispersions of drug in polymers are widely used to obtain the amorphous state of materials. However amorphous is unstable and easily crystallized. An estimation method for the physical stability of amorphous drug and a clarification of the effect of polymer on crystallization of amorphous drug in solid dispersion are primarily required. Generally solid dispersions were containing different ratios of drug and polymers, e.g. Polyvinylpyrrolidone (PVP), Hydroxypropylmethylcellulose (HPMC). The physical stability of solid dispersion was evaluated by the induction period of the crystallization under isothermal condition. The induction period of crystallization from amorphous drug was gradually delayed with increasing amounts of polymer. The crystallization of drug was prevented by the present of polymer. Drug-polymer interaction was recognized as one of the central cause, and the FT-IR spectra of solid dispersion suggested the interaction between drug and polymer. In spite of no interaction between Flurbiprofen and PVP, the solid disperseon containing them was stable. It is noted that the interfacial free energy between drug crystal and supercooled liquid and the activation energy of diffusion of drug molecules which related to nucleation was closely related to the drug crystallization. In the case of tolbutamide or flurbiprofen and PVP, the interfacial free energy was not affected by PVP contents. The activation energy of diffusion was increased with increase the PVP contents in the solid dispersion, suggesting that the crystallization of TB in solid dispersion would be affected by the diffusivity of drug. On the other hand, in the solid dispersion of FBP, the activation energy of diffusion was not changed by PVP contents. These reports suggested that the retardation of crystallization of drug induced by the coexistense of polymer could be related to the interaction between drug and polymer and the increase of the activation energy of diffusion.
