Continuous Separation of Isomers in Fluidized Bed Crystallizers

Abstract

A fluidized bed process exploiting two coupled crystallizers was studied for continuous preferential crystallization in two ternary systems, namely, ortho-aminobenzoic acid (OABA)/para-aminobenzoic acid (PABA)/water and L-asparagine monohydrate (L-asn•H 2 O), D-asparagine monohydrate (D-asn•H 2 O)/water. A continuous supply of seeds was realized by ultrasonic comminution of crystals, withdrawn from the bottom of the partially conical-shaped fluidized bed crystallizers. Product removal occurred via outlets placed at specific positions in the conical sections of the crystallizers. The crystal size distribution (CSD) as well as the purity of the product crystals reached steady states with purities exceeding 97%. A simplified dynamic model was developed and applied to predict solution concentrations and product CSDs. Results of primary solid−liquid equilibria and metastable zone width studies are also reported.

Effect of additives on the preferential crystallization of L-asparagine monohydrate

“…The solubility and metastable zone width of L-Asn•H2O, DL-Asn•H2O and LAsn•H2O with 5% additives is shown in Figure 2 [27]: however that study is over 80 years old, and perhaps the purification of the amino acids was more difficult at that point. Solubility data over the entire range of temperatures measured agree very well with the recent data of Binev et al [28]. This is curious since both studies used identical techniques and equipment (the Crystal16, multiple reactor system).…”

Diastereomeric salt crystallization of chiral moleculesvia sequential coupled‐Batch operation

“…This approach allows for a comparatively small operating region, which avoids excessive cooling of the mother liquor and prevents attainment of the thermodynamically stable composition due to primary nucleation of the counter salts . This method was extended for use in coupled fluidized beds where the formation of secondary nuclei is suppressed, thus extending this operating window and process robustness significantly as fines destruction of any unwanted primary nuclei can be easily implemented to dissolve any enantiomer in the incorrect tank following primary nucleation . Traditionally, this may have been difficult to implement industrially in the pharmaceutical industry which has almost exclusively utilized standard batch equipment.…”

Self‐Reporting Inhibitors: A Single Crystallization Process To Obtain Two Optically Pure Enantiomers

“…Completely isolation of the crystallization processes of two enantiomers can be realized. The performances are significantly better than the state‐of‐the‐art methods, although this strategy only works in the case of conglomerates at this stage and the productivity should be further improved in practical applications . It might allow the development of more efficient fractional crystallization methods and the chiral separation on different scales.…”