Cooling crystallization of paracetamol in hollow fiber devices

We examine here cooling crystallization of aqueous paracetamol solutions in hollow fiber devices. It is shown that a solid hollow fiber crystallizer (SHFC)-static mixer assembly can be operated successfully up to 30-40°C below the metastable zone limit. Such a capability is not existent in industrial cooling crystallizers; it allows the decoupling of nucleation and growth, an opportunity offered currently only by impinging jet mixers for antisolvent crystallization. In addition, it leads to the achievement of very high nucleation rates and hence small crystal sizes. The former were 2-4 orders of magnitude higher than values previously obtained in solid hollow fiber crystallizers for potassium nitrate and salicylic acid and reached values encountered only in impinging jet crystallization. A qualitative comparison with existing literature data showed that the SHFC-static mixer combination confined the crystal size distribution (CSD) to smaller sizes and a narrower range. Finally, a linear relationship between the mean crystal size and the cooling medium temperature was observed. This relationship is indicative of the simplicity available in SHFCs vis-à-vis CSD control.