Thermally sensitive APIs and pharmaceutical class polymers are processed via twin screw extrusion to increase the bioavailability of the API of the dosage form. In early stage development, very limited (and expensive) amounts of materials are available. Hence, atypical twin screw extruder geometries are used to process small batches of less than 50 gm to test the feasibility of a formulation. If deemed viable, scale-up to more conventional twin screw configurations is the next step. Studies were performed to optimize the processing of meloxicam (MLX), a thermally labile drug with copovidone (VA64), a water soluble, pharmaceutical grade polymer. Initial studies were performed on a nano-16 co-rotating twin screw extruder with 1.2 OD/ID ratio, then a ZSE-18 co-rotating twin screw extruder with 1.5 OD/ID ratio, and then a ZSE-27 counter-rotating twin screw extruder with 1.5 OD/ID ratio. Once the mixing mechanism and boundary conditions were understood, successful scale-up was the result. The scale-up methodology and results will be presented.