Evaporation crystallisation process

The number of inputs which are available for controlling crystallisation processes is limited. Possible Inputs for a continuous evaporative crystallisation process are, crystalliser temperature, residence time and rate of evaporation. These Inputs affect the crystal size distribution (CSD) through overall changes in the nucleatlon rate, the number of new crystals per unit time, and the growth rate, the increase in linear size per unit time, and therefore do not discriminate directly with respect to size. Moreover, it has been observed that, for a 970 litre continuous crystalliser, the effect of the residence time and the production rate is limited. Size classification, on the other hand, does allow direct manipulation of the CSD. 

This highly purified substance may contain up to 3% of a diastereomeric impurity. By using an evaporative crystallisation process that exploits subtle solubility differences between the parent compound and the diastereomer, this impurity level is reduced to < 1 % and the API is isolated as a white crystalline solid. The final pharmaceutical grade cGMP drug substance is obtained in >98% purity with overall 50% recovery from the crude extract. 

Simultaneous heat and mass transfer also occurs in drying processes, chemical reaction steps, evaporation, crystallisation, and distillation. In all of these operations transfer rates are usually fixed empirically. The process can be evaluated using either the heat- or mass-transfer equations. However, if the process mechanism is to be fully understood, both the heat and mass transfer must be described. Where that has been done, improvements in the engineering of the process usually result (see Process energy conservation). 

In some applications such as catalytic hydrogenation of vegetable oils, slurry reactors, froth flotation, evaporative crystallisation, and so on, the success and efficiency of the process is directly influenced by the extent of mixing between the three phases. Despite its great industrial importance, this topic has received only limited attention. 

With the help of the solubility data given on page 299, it is also possible to follow the crystallisation process in a quantitative manner, and to calculate the amounts of the salts successively deposited on isothermal evaporation. Thus, when a solution containing i gram-molecule of potassium sulphate (174 3 grams) and i gram-molecule of... 

SFE must be seen within a group of separation processes which are well known, widely used, and sufficiently well understood. These processes comprise the various forms of distillation (rectification), evaporation, crystallisation, liquid- liquid extraction,... 

The selection criteria for a compound used in a cooling process include low solution concentration W (g compound/lOOg water) at 25°C and high solubility parameter SP. Cooling crystallisation is only profitable if the saturated concentration C (kmole/m solution) satisfies the equation defining the SP (Mersman 2001). The temperature Tk is in degrees Kelvin. When the solubility-temperature curve is flat, evaporative crystallisation must be applied. 

A typical design feature is the way supersaturation is controlled and kept within the metastable range. The method is independently from the crystallisation process. Figure 9.6 explains this method based on the vacuum cooling crystallisation principle. This principle is also valid for the vacuum evaporation, surface cooling and reaction crystallisation. 

By passing hydrochloric acid into the ethereal solution of the hydrocarbon a solid chloride was obtained, which, after evaporation of the ether, crystallised out in needles from the reddish-blue residue. The crystallising process of the chloride was materially facilitated by a slight addition of alcohol and the application of a freezing mixture. The product, after being crystallised once, melted at 68 to 70 . The melting-point of a sample which had been repeatedly recrystallised from methyl alcohol was found to be 72 to 74 . 

The recovery of the product is described in outline in Figure 95. Essentially the process involves separating the broth and mycelium by filtration, extracting the mycelium with acetone and methylene chloride. Combining these extracts with the broth and re-extracting with methylene chloride. The extract is washed with 2% sodium bicarbonate, evaporated and re-dissolved in methylene chloride. The product is allowed to crystallise from the methylene chloride. 

On an industrial scale, evaporation and crystallisation are the main processes used for the recovery of dissolved solids from solutions. 

The problem of selecting the most appropriate operation will be further complicated by such factors as the concentration of liquid solution at which crystals start to form. Thus, in the separation of a mixture of ortho-, meta-, and para-mononitrotoluenes, the decision must be made as to whether it is better to carry out the separation by distillation followed by crystallisation, or in the reverse order. The same kind of consideration will arise when concentrating a solution of a solid then it must be decided whether to stop the evaporation process when a certain concentration of solid has been reached and then to proceed with filtration followed by drying, or whether to continue to concentration by evaporation to such an extent that the filtration stage can be omitted before moving on to drying. 

---