Effect of carbamazepine on viscoelastic properties and hot melt extrudability of Soluplus®

The purpose of this study was to apply viscoelastic properties of polymer and drug-polymer mixtures to determine processing conditions for the preparation of amorphous solid dispersion by melt extrusion. A poorly water-soluble drug, carbamazepine (CBZ), was mixed with Soluplus (R) as the carrier. Torque analysis using a melt extruder was performed at 10,20 and 30% w/w drug concentrations and the effect of barrel temperature was studied. Viscosity of the mixtures either at fixed temperatures with different angular frequencies or as a function of temperature with the same frequency was studied using a rheometer. The viscosity of Soluplus (R) and the torque exerted on the twin screws decreased with the increase in CBZ concentration. The viscosity versus temperature plots for different CBZ concentrations were parallel to each other, without the drug melting transition, indicating complete drug-polymer miscibility. Thus, the drug-polymer mixtures could be extruded at temperature as low as 140 degrees C with 10% w/w drug load, 135 degrees C with 20% w/w drug and 125 C with 30% w/w drug, which were, respectively, similar to 50 degrees C, 55 degrees C and 65 degrees C below the melting point of 191 degrees C for CBZ. The differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) analyses of the binary mixtures extruded at 125-150 degrees C showed absence of crystalline drug. A systematic study of miscibility and extrudability of drug-polymer mixtures by rheological and torque analysis as a function of temperature will help formulators select optimal melt extrusion processing conditions to develop solid dispersions. (C) 2014 Elsevier B.V. All rights reserved.