Poorly water-soluble drug substances that exhibit high melting points are difficult to process by melt extrusion due to chemical instability at high temperatures required for processing. The purpose of this study was to extrude meloxicam (melting point 255 °C) by optimizing processing parameters and formulation composition. Five extrusion studies were performed: 1) design space, 2) impact of moisture, 3) impact of melt residence time, 4) specific energy optimization, and 5) altered microenvironment pH. Powder X-ray diffraction and polarized light microscopy were used to confirm amorphous conversion. Liquid chromatography-mass spectrometry was used to characterize the extrusion degradation pathway. The formulation consisted of 10% meloxicam and 90% copovidone. When processed above 140 °C, significant chemical degradation was observed. The minimum energy input to convert meloxicam was 1.8 kW h/kg. Degradation of meloxicam during extrusion was identified as hydrolysis. Barrel configuration and screw design were designed to drive-off moisture and reduce melt residence time. With optimized parameters, the purity of the extrudate was 96.7%. To further enhance chemical stability, meglumine was added to provide a stabilizing basic microenvironment resulting in 100% purity. By process parameter optimization and formulation modification, we successfully extruded a meloxicam amorphous solid dispersion.