Improvement of dissolution and tabletability of carbamazepine solid dispersions with high drug loading prepared by hot-melt extrusion

摘要

Solid dispersions (SDs) have made great progress in the improvement of dissolution for poorly soluble drugs, however the low drug loading still limits their wide application. In the present paper, high carbamazepine (CBZ) loaded SDs with excellent dissolution and tabletability wereprepared and characterized. The CBZ SDs were prepared with Eudragit EPO as carrier by hot-melt extrusion (HME) in the drug: carrier ratio of 4:1. Powder X-ray diffraction, differential scanning calorimetry, fourier transform infrared spectroscopy and powder dissolution was carried out to characterizethe SDs. The results showed that the crystalline form the polymorph of CBZ in SDs was transformed into form I from form III after extruded at 140 °C. Wettability and microstructure of CBZ SDs were improved by the HME process, which promoted the dissolution significantly. More than 85 %drug dissolved within 5 min from CBZ SDs with even only 20 % Eudragit EPO as carrier. CBZ SDs tablets were prepared by direct tableting with a universal material testing machine at various compaction pressures. Compactibility and tabletability were enhanced significantly by the HME process.All of these results showed the CBZ SDs prepared by HME with 80 % CBZ and 20 % Eudragit EPO could improve the dissolution and tabletability significantly.