Continuous manufacturing of high quality pharmaceutical cocrystals integrated with process analytical tools for in-line process control

Moradiya, Hiren G. and Islam, Muhammad T. and Scoutaris, Nikolaos and Halsey, Sheelagh A. and Chowdhry, Babur Z. and Douroumis, Dennis (2016) Continuous manufacturing of high quality pharmaceutical cocrystals integrated with process analytical tools for in-line process control. Crystal Growth and Design, 16 (6). pp. 3425-3434. ISSN 1528-7483

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    Abstract

    A continuous manufacturing process for pharmaceutical indomethacin–saccharine cocrystals was achieved by extrusion processing with high throughput. Down-stream milling and blending of the extrudates was followed by feeding the formulated cocrystals in a capsule-filling machine. By applying a quality by design approach, the process was optimized and scaled up to produce 3000 capsules/h of pharmaceutical cocrystals. Process analytical tools such as near infrared reflectance and spatial filter velocimetry probes were coupled at various process stages for in-line monitoring and quality control. Further physicochemical characterization of extruded batches confirmed the manufacturing of high quality cocrystals. A fully integrated continuous process starting from raw materials to produce a finished product was assembled with only six unit operations and a small footprint. The study is a paradigm of continuous manufacturing of pharmaceutical cocrystals.