Crystallization cycle

In the case of complex crystallization cycles of cocoa butter, the two preceding examples have shown that the macroscopic approach of the FEM-TTT model allowed a satisfactory prediction of the crystallization kinetics. The model simply needs to first establish the TTT diagrams corresponding to the experimental conditions used. Therefore, computer modeling can become a tool for quantitative simulation of the crystallization kinetics of fat (e.g., estimation of percentage of phases formed and crystallization times) under complex cooling and shear conditions. 

In the pharmaceutical industry most solid compounds are crystallized in batch operations, i.e., the crystalline product is isolated at the end of the operating cycle. Many bulk chemicals, such as table sugar, are prepared through continuous processes, in which the product is collected throughout the crystallization cycle. Batch crystallization produces a narrower range of particle size and may afford better control for the efficient crystallization of molecules from complex mixture [14]. 

Similar to the process described in Option 1 above, the antibiotic is first dissolved in a solvent mixture of acetone/water and frozen at a temperature of — 40 C. The freeze crystallization cycle is then started by raising the temperature to between — IO C and — 30°C and holding the system for... 

Table 11-2 Freeze Crystallization Cycles (All Acetone Levels)...

Table 11-2 shows the freeze crystallization cycles for the study. Three different freeze crystallization temperatures, — IO C, — 2() C, and — 30°C, and three different levels of acetone, 10vol%, 20 vol%, and 30 vol%, were studied. The output variables were the degree of crystallization of imipenem products and the percentage of the liquid phase at the freeze crystallization temperature. For the aging time of stage 3, a value of 99.95 hours was shown in order to hold the freeze dryer shelf temperature at —40°C overnight. 

During the crystallization cycle, all the vessels are sampled many times in a sequential manner and at the end of the analysis there are enough temperature-concentration data points for each resin to properly draw the cumulative curves, as shown in Fig. 24, with the simultaneous analysis of five LLDPE resins of different density. The complete dissolution and crystallization analysis of five samples can be carried out simultaneously in around 7 h in a fully automated way. 

Both techniques share the same principles of fractionation on the basis of crystallizability. TRFF is carried out in a packed column and demands two full temperature cycles, crystallization and elution (dissolution), to obtain the analysis of the composition distribution. In CRYSTAF, the analysis is performed in a single step, the crystallization cycle, which results in faster analysis time and simple hardware requirements. 

CEF analysis follows similar steps as in TREF, but during the crystallization cycle a small solvent flow, FC, is passed through the column in such a way that when molecules of a given composition reach their crystallization temperature, they are segregated from solution and anchored on the support. Meanwhile, the... 

Other components of lower crystallinity, still in solution, move along the column until they reach their own crystallization temperature. At the end of the crystallization cycle, the three composition families shown in Fig. 26b are physically separated inside the column according to crystallizability this process is referred to as dynamic crystallization and can separate components in a similar fashion as CRYSTAF although all polymer molecules still remain inside the column in three different locations. 

The organic melt is emulsified in water with the aid of a suitable nonionic agent and stabilized by a protective colloid, e.g. potato starch gelatinized with water. The system is crystallized by cooling, and the crystals are separated from the emulsion and washed with water. The operation may be repeated if required. A typical example is shown in Figure 8.57 where five or six emulsion-crystallization cycles yield an almost pure naphthalene at an overall yield of 70 per cent compared with a less pure product at a 2 per cent yield by seven conventional fractional crystallization steps. The high efficiency of the emulsion crystallization is apparently due to the fact that crystal agglomeration does... 

Figure 8.57. Comparison of fractional and emulsion crystallization cycles for the purification of naphthalene. After Holed, 1965)...

Now, if dissolution was effected at an intermediate temperature, 37°C, an isotherm having an intermediate shape and position was obtained (Figure 6.19, curve c). The crystals, while essentially free from degenerate forms, were rather more heterogeneous in size than for 7 = 35°C. Repetition of the dissolution-crystallization cycle gave a curve (filled circles) which was consistent with an increase in the concentration of nuclei N at least the first part of the isotherm was superimposable on curve b by shifting the log t axis. 

The absolute asymmetric synthesis described above is a stochastic process, as the probabihty of obtaining either a left- or a right-handed crystal, in different experiments, is identical. At the authors laboratories, attempts have been made to extend the absolute asymmetric synthesis into autocatalytic cycles, where the presence of a product formed in a given enantiomorphous crystal could induce -by ensuing fresh crystallizations cycles comprising crystallization/dissolution - the formation of crystals of the same handedness as in the first crystal formed by chance. In this way, the handedness generated in the first stochastic experiment would be both preserved and efficiently proliferated in the ensuing fresh crystallization experiments (Scheme 8.7). 

Scheme 8.7 Schematics of an absolute asymmetric synthesis by autocatalytic cycles of crystallization coupled with reaction, where the presence of a product formed in a given enantiomorphous crystal could inhibit the formation of its parent crystals in ensuing fresh crystallization cycles leading to the formation of crystals of the opposite handedness.

Figiue 2. The generalized temperature curve for a salt crystallization cycle. 

The melting-crystallization cycle of an oriented network that is conducted under equilibrium conditions results in a reversible contractile system when the force is held fixed. Alternatively, large changes in the tension are observed when the length is held constant. These two complementary observations are inherent properties of all types of macromolecular systems. The above analysis has been limited to apure one-component homopolymer of uniform cross-section. However, it can be extended, in a straightforward manner to include inhomogeneous fibers, copolymers, and polymer-diluent mixtures.(4)... 

As pointed out by Monrabal and coworkers, the TREF is an operational complex method requiring more than one day to perform. The CRYSTAF method is also a separation method that fractionates samples of differing crystallizability by slowly cooling a polymer solution in a single crystallization cycle by monitoring the decrease in solution concentration as the temperature is lowered. Because of this one-step approach, analysis time is reduced to around 6 hours for five simultaneous samples [23]. 

Crystallization Analysis Fractionation (CRYSTAF) It is based on the segregation of crystals of different morphology or comonomer content by crystallization, In CRYSTAF, the separation and analysis are performed in a single step (the crystallization cycle), where concentration of the polymer solution is intermittently sampled and analyzed as the temperature goes down. The temperature-concentration data which are obtained correspond, in the cases of branched poly(olefins) or their copolymers with a-olefins, to the cumulative curve of the side chain branching distribution (SCBD). The last point at the lowest temperature of the experiment is the soluble or noncrystallizable fiaction. 

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