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Designing Continuous Crystallization Platforms

A continuous crystallization platform was developed that allowed Process Analytical Technologies (PAT) to be applied in situ via the use of novel flow cells. This crystallization platform was used to develop the anti-solvent crystallization of benzoic acid from aqueous ethanol solution. 2, 3 The equivalent tank based Mixed-Suspension, Mixed-Product-Removal (MSMPR) crystallization was also characterized using PAT in a continuous stirred tank utilizing a pneumatic slurry transfer technique. 1,4,5 These continuous crystallizations were compared to the equivalent batch crystallizations so that a true measure of performance of the continuous crystallizations could be made. 1 As expected the continuous crystallizations offered hugely intensified production with approximately the same amount of material generated by a ~40 ml plug flow, 9 L MSMPR and 42, 10,000 L batch crystallizations per annum. Furthermore, the alternate process dynamics and mixing environments offered by the plug flow and MSMPR enabled a wider range of particle sizes and morphologies to be produced than would be available if only the batch crystallization options were considered. 1,3 Use of in situ PAT permits significant reductions in process development time and can also be applied to monitoring and control of continuous industrial crystallizations. It is hoped that such methods can facilitate the inclusion of continuous crystallizer configurations in standard pharmaceutical commercialization procedures. Guest

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