Abstract:
Solid dispersions (SDs) is one of the main technologies to improve the dissolution of poorly soluble drugs in drug research and development. However, supersaturated high-energy amorphous state drug in SDs is often associated with a tendency to recrystallize during long term storage. The carrier of SDs plays a key role in maintaining the amorphous state of the drugs. Traditionally, screening of carrier in the development process is a time-consuming process. The effects of polymer carriers on the long-term physical stability of the amorphous state of Erlotinib (ERL) in SDs were studied. ERL SDs were prepared with different ratios of hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinylpyrrolidone (PVP), poly(vinylpyrrolidone-co-vinyl-acetate) (PVP/VA), Eudragit, and Soluplus by solvent evaporation method. On the basis of the Flory-Huggins interaction parameter (χ) and anti-solvent microscopic observations, the compatibility of the polymer with ERL and polymer's influence on the crystallization of ERL were predicted. Focused Beam Reflectance Measurement (FBRM) system was used to analyze the morphological effect of the polymer on the crystallization process. Then the amorphous state formed by different proportions of SDs were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The physical stability of amorphous state of SDs in accelerated test condition were determined by PXRD. The results indicate that HPMC is a suitable carrier for the preparation of ERL amorphous SDs. The combination of the interaction parameter χ, anti-solvent microscopic observation and FBRM analysis is an effective way for the selection of a suitable carrier for amorphous SDs. The understanding of the impact of polymers on amorphous SDs would be beneficial for the rapid development of poorly soluble drugs.