Preparation and Characterization of High Carbamazepine-loading Solid Dispersion / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare high carbamazepine (CBZ) loading solid dispersion and investigate its solubilization mechanism and stability. METHODS: The effects of different drug-carrier ratios and preparation METHODS on dissolution were investigated by intrinsic dissolution rate. The existing form of CBZ in the solid dispersion was characterized by differential scanning calorimetry(DSC) and powder X-ray diffraction(PXRD). The micromorphology was observed with scanning electron microscopy and the solubilization mechanism was probed by wettability test and particle size measurement. RESULTS: The solid dispersion prepared by hot-melt extrusion with the drug/carrier ratio of 4∶1 demonstrated the highest dissolution, which was 327 fold that of the untreated drug. CBZ in the solid dispersion was small crystalline which had been transformed from polymorph III to . Wettability of the solid dispersion in hydrochloric acid solution was increased significantly, which could be rapidly dispersed into a nanometer-sized suspension. The solid dispersion was very stable without any changes for more than 6 months under accelerated test conditions. CONCLUSION: The CBZ solid dispersion with 80% drug loading prepared by hot melt extrusion with a hydrophilic polymer, Eudragit EPO, as carrier possesses satisfactory properties such as fast drug dissolution and excellent stability.