(281b) Combined Impact of Process Parameters Temperature, Pressure, and Shear Stress on Polymorphism in Crystalline Solid Dispersion

Understanding the processing requireto generate crystalline solid dispersions (CSDs) containing metastable polymorphs

the application of hot-melt extrusion (HME) and 3D printing (3DP) as polymer-based formulation approaches. Hence, to successfully implement CSDs as alternative solid dosage formulations, the effect of critical process parameters (CPPs) on potential polymorphic phase transformations (PPTs) needs to be examined. This study extends the current knowledge on the influence of CPPs, through temperature-pressure-shear simulated extrusion (TPSS-E) using the model system flufenamic acid (FFA) in polyethylene glycol (PEG). The TPSS-E results revealed a significant reduction in the average PPT induction time (53 %) compared to previous temperature-pressure simulated extrusion (TPS-E) studies without shear stress. However, TPSS-E control experiments performed at 25°C did not show any PPT. uggestthat temperature is the most critical parameter on determining whether a PPT will occur, while pressure and shear stress significantly accelerates the PPT from the metastable () to the stable form ( at elevated temperatures. These results demonstrate thatand it is possible to control the metastable polymorph in CSDs during extrusion processes if the thermodynamic and kinetic boundaries, the CPPs, and material attributes of the drug-polymer system are well understood and controlled. Ththe application of HME and 3DP as polymer-based formulation strategies for CSDs containing metastable polymorphs.