Preparation and characterization of carbamazepine-polyethylene oxide hot-melt extruded solid dispersions

Abstract

The aim of the presented study was to investigate the possibility of usage of polyethylene oxide polymer (PEO, Polyox® WSR 301, DOW, USA) in the preparation of carbamazepine hot-melt extruded solid dispersions. Hot-melt extrusion (HME) is a simple, solvent free and continuous processing technique used to produce variety of dosage forms. Thermoplastic materials, such as PEO polymers, are required for the process feasibility. Poloxamer 407 (Lutrol® F127, BASF, Germany) was used as a plasticizer to facilitate the HME process, by reducing the processing temperature and lowering the monitored torque. Physico-chemical properties of carbamazepine and polymers, their physical mixtures and dispersions made by melt-mixing or HME were characterized in detail. A hot-melt extruder with one rotating screw was used for the preparation of solid dispersions by HME technique (RCP-0250 Microtruder, Randcastle extrusion systems, USA). Samples were analyzed by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), FT-IR spectroscopy and hot-stage microscopy (HSM) methods. Obtained results indicate that the addition of plasticizer enables preparation of carbamazepine-PEO hot-melt extrudates using a single-screw extruder configuration. It was demonstrated that there is no degradation of CBZ upon heating in the HME processing temperature range (90-110°C). Furthermore, the crystalline form of CBZ was not altered during the HME processing. The presence of CBZ form III crystals, homogeneously dispersed in the hot-melt extrudates, was confirmed. Dispersion of CBZ crystals in the polymers mixtures was visualized using the polarizing HSM technique. Presented study demonstrates the potential of PEO WSR 301 application in the preparation of carbamazepine hot-melt extruded solid dispersions.