Predicting melt rheology for hot-melt extrusion by means of a simple T-measurement.

The feasibility of predicting melt rheology by using the glass transition temperature (T) of a desired amorphous solid dispersion (ASD) for hot-melt extrusion (HME) and other melt based processes is presented. Three groups of three different active pharmaceutical ingredients (APIs) or plasticizer/copovidone mixtures, with identical glass transition in rheological testing, were used. Their rheological behavior as a function of temperature and frequency were analyzed by means of small amplitude oscillatory shear (SAOS) on an oscillatory rheometer. The zero-shear viscosity (η) identified at 150°C was compared to T, measured by differential scanning calorimetry (DSC) and SAOS. A strong correlation between η and T was identified, independent of the API or plasticizer used to achieve T of the mixture. To evaluate and rate the discrepancy in η of the different mixtures at same T, hot-melt extrusion trials were conducted to measure torque and mean residence time. In this paper, carbamazepine, dipyridamole, indomethacin, ibuprofen, polyethylene glycol (PEG 1500) in vinylpyrrolidone-vinyl acetate copolymer (copovidone) as matrix polymer were used.