Diffusivity of amorphous drug in solid dispersion

Filmy solid dispersion of terfenadine (TFD), fenofibrate (FFB), and carbamazepine (CBZ) and methacrylic acid methyl methacrylate copolymer (Eudragit ® ) was prepared by evaporating their solution. Raman and IR measurements for the filmy samples were performed. Concentration profile of TFD, FFB, and CBZ in solid dispersions was evaluated by their characteristic peaks, and then their diffusion rate constants were calculated. The start point of the crystallization peak under isothermal condition was determined by XRD–DSC. Viscoelastic character of Eudragit ® was evaluated by dynamic mechanical analysis (DMA). The distribution map of drugs in their solid dispersions showed the diffusion state of drugs during storage. The concentration profile of TFD, FFB, and CBZ in the solid dispersion was calculated from obtained mapping data. The diffusion rate constant of both drug in Eudragit ® EPO was higher than that in Eudragit ® RLPO. The induction period of crystallization from amorphous CBZ was gradually delayed with increasing amounts of Eudragit ® . The IR peak due to C=O was shifted to higher wave number; it suggested that there were some molecular interactions between CBZ and Eudragit ® . From the results of the change in the interaction of drug-Eudragit ® , it may be concluded that the diffusivity of drug molecule in polymer closely related to the delay of the induction period of crystallization of amorphous. DMA measurement clarified the difference in the viscosity of Eudragit ® having different functional groups and molecular mass. These results suggested that the retardation of crystallization by Eudragit ® could be related to the sample viscosity.