Continuous crystallizer selection

Preferential Removal of Crystals. Crystal size distributions produced ia a perfectiy mixed continuous crystallizer are highly constraiaed the form of the CSD ia such systems is determined entirely by the residence time distribution of a perfectly mixed crystallizer. Greater flexibiUty can be obtained through iatroduction of selective removal devices that alter the residence time distribution of materials flowing from the crystallizer. The... 

R)P Menthyl Methylphenylphosphinate (I) (10). The (R)P isomer was obtained from the Mislow diastereoisomeric mix (50/50) by selective seeding from a 50% solution in a- or / -pinene. The best procedure is to continue crystallizing several samples until light feathery crystals appear. Once separated, these feathery crystals are further purified by crystallization from hexane. Suitable material melted at 86°-87°C, [< ]D20 — 17.2 (c = 1 in C6H6). [Mislow m.p. 89°C, [a]D20 — 16]. 

Curve 4 exhibits very steep solubility. Yield is obtained by cooling the feed solution. To prevent fines formation, the cooling must exactly follow the solubility curve. This is done automatically in batch crystallizers. Continuous crystallizers in series must have the crystallizer stage temperatures selected so as not to cross the solubility curve. Benzoic acid and DMT exhibit this type of solubility. 

As shown in Fig. 11.1-1, the solids—liquid separation device is the link between the solids formation equipment and the diying operation, Thus, predictable and reliable operation is essential in this stage of the processing sequence. Continuous or baich-automatic centrifuges nad continuous vacuum filters are typically used to recover solid material from continuous crystal I ization operations. Many factors are considered in [ha final selection of the device. In any case, an equipment testing program is always essential to determine the capacity and performance of solids separation equipment. 

Obviously, there are many different configurations of batch and continuous crystallizers. The design used for a particular chemical system must be selected in light of the nature of the material being crystallized and the desired properties of the product, such as purity, habit, and CSD. For simplicity, the discussion... 

To be able to select a crystallization temperature in the single liquid phase region at a given amine fraction, the liquid-liquid equilibrium lines of the amine-water-NaClsat systems were determined. To establish to what extent an antisolvent reduces the sodium chloride solubility and to calculate the maximum obtainable magma densities during crystallization, sodium chloride solubilities in the amine-water mixtures were measured. Finally continuous crystallization experiments were carried out and the feasibility of an antisolvent recovery by a temperature increase was investigated. 

With the amine-H20-NaClsat liquid-liquid equilibrium lines the conditions were selected for the continuous crystallization experiments in the single liquid phase area. The experiments with DMiPA were carried out at Xomipa = 0.1, 0.3, 0.6 and 0.9 at a temperature of 5 C. With DiPA sodium chloride was crystallized at Xehpa = 0.9 and T = 1 °C (all the amine concentrations are expressed as salt free weight fractions). 

Computational methods could, therefore, potentially impact on polymorph screening, salt or co-crystal selection, as well as the avoidance of solvates. The outline of such a possibility should not be viewed as an over-optimistic assessment of current capabilities, but rather a goal towards which developments should aim. Given that progress is being made on flexible molecules and multi-component crystal structures, the methods that are necessary for such in silico screens are attainable, although it is difficult to predict the rate of progress and, therefore, when such calculations will be practical for the typical pharmaceutical molecule. Moreover, results will always need to be interpreted with care and a realistic view of the approximations and limitations of the methods. This is where continued assessment of methods on well-characterized systems is needed, to inform our level of confidence in the calculations. 

In this section, the principles involved in using a population balance to describe the crystal size distribution in the product from a well-mixed continuous crystallizer are illustrated. The primary objective of this treatment is to show how nucleation and growth kinetics can be evaluated from data on the crystal size distribution produced in such crystallizers. Detailed development of the theory and extensions of these principles to crystallizers that employ selective removal of crystals from the crystallizer internals or to batch or transient continuous crystallizers is provided by Randolph and Larson. ... 

In selected cases, the effect of solvation on the crystalline structure formed is, however, considerably more pronounced. For example, the observed packing in the crystal of 2,4,6-tris( 1,3-propylenediamine-N,N -)cyclotriphosphazene (4) dihydrate (Fig. 6) is due to strong intermolecular hydrogen bonds between molecules of water and suitable couples of N-H groups on the host moiety M). The HzO species form also continuous H-bonded layers of solvation around the cyclophosphazene derivatives, thus stabilizing the crystal lattice. 

Furthermore, all the examples shown above in Sects. 4.1-4.3 emphasize the significance of both steric and functional features in selective crystallizations. The latter are needed not only for binding between the individual host and guest constituents, but also for effecting a continuous and relatively unflexible pattern of intermolecular arrangement in the crystal lattice. This observation appears to be a very useful one in the systematic design of novel clathrate-based synthetic receptors. 

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