The feasibility of upscaling the formulation of co-amorphous indomethacin-lysine from\nlab-scale to pilot-scale spray drying was investigated. A 22 full factorial design of experiments (DoE)\nwas employed at lab scale. The atomization gas flow rate (Fatom, from 0.5 to 1.4 kg/h) and outlet\ntemperature (Tout, from 55 to 75 Degree Centigrade ) were chosen as the critical process parameters. The obtained\namorphization, glass transition temperature, bulk density, yield, and particle size distribution were\nchosen as the critical quality attributes. In general, the model showed low Fatom and high Tout to\nbe beneficial for the desired product characteristics (a co-amorphous formulation with a low bulk\ndensity, high yield, and small particle size). In addition, only a low Fatom and high Tout led to the\ndesired complete co-amorphization, while a minor residual crystallinity was observed with the\nother combinations of Fatom and Tout. Finally, upscaling to a pilot scale spray dryer was carried out\nbased on the DoE results; however, the drying gas flow rate and the feed flow rate were adjusted to\naccount for the different drying chamber geometries. An increased likelihood to achieve complete\namorphization, because of the extended drying chamber, and hence an increased residence time of\nthe droplets in the drying gas, was found in the pilot scale, confirming the feasibility of upscaling\nspray drying as a production technique for co-amorphous systems.
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