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.
- continuous manufacturing
- process analytical technologies (PAT)
- in-line process control
- near infrared reflectance
- spatial filter velocimetry probes
Moradiya, H. G., Islam, M. T., Scoutaris, N., Halsey, S. A., Chowdhry, B. Z., & Douroumis, D. (2016). Continuous manufacturing of high quality pharmaceutical cocrystals integrated with process analytical tools for in-line process control. Crystal Growth and Design, 16(6), 3425-3434. https://doi.org/10.1021/acs.cgd.6b00402