Rheological modeling and torque-based processability prediction for celecoxib/PVPVA hot-melt extruded amorphous solid...

Predicting the processability of amorphous solid dispersions (ASDs) during hot-melt extrusion (HME) remains critical in pharmaceutical development. This study demonstrates that melt apparent viscosity data obtained from rotational rheology, combined with constitutive modeling, can be extrapolated to approximate in-process extruder torque and thereby guide formulation and process selection. Using celecoxib-PVPVA 64 as a model system, composition- and temperature-dependent melt rheology was quantified for three drug-to-polymer ratios (30/70, 50/50, 70/30 w/w) over 130 - 160 °C. Steady-shear viscosity data of vacuum compression moulded ASDs were fitted to Cross and Carreau models and extrapolated to a process-relevant shear rate corresponding to 100 rpm screw speed. Extrapolated viscosities were converted into torque using screw-channel shear stress relationships, and an empirical exponential calibration was applied to reconcile calculated and experimental torque under starve-fed HME conditions. Polymer-rich formulations (30/70) showed the highest apparent viscosity and torque demand, whereas drug-rich systems (70/30) exhibited lower viscosities and torque due to celecoxib plasticization, at the expense of a reduced amorphous processing window. Across most conditions, the Cross model provided superior viscosity fits and marginally better torque predictions than the Carreau model. Transparent filaments for the 30/70 and 50/50 formulations confirmed successful amorphization, whereas the 70/30 formulation yielded opalescent filaments consistent with incipient phase heterogeneity. Among the investigated formulations, the CCX/PVPVA ASD prepared at 30:70 under 150 oC showed the most favorable balance of homogeneous dispersion, solid-state amorphization, and processability, and was therefore identified as the best formulation and process setting for VCM preparation. Overall, this viscosity-to-torque framework offers a material-sparing approach to anticipate HME processability and define composition- and temperature-dependent processing windows for ASD formulations.