Reactive antisolvents

Antisolvent and Reactive Crystallization with In-Line Mixing... 

Effect of feed pipe location (for antisolvent and reactive crystallizations) (see Section 6.6.1.5 below). 

Another key factor in successful pilot plant and manufacturing plant operation is the appropriate use of subsurface addition of antisolvents and reactive reagents for crystallization and precipitation. The primary purpose of subsurface addition is the introduction of the agent causing supersaturation in the region of intense micromixing in the vessel to avoid local excess supersaturation with the associated potential for increased nucleation. 

The mixing texts referenced above contain extensive discussion of the importance of the location of feed streams. While these studies are primarily concerned with reagent feed for chemical reactions and the influence of local turbulence on reaction selectivity, the same issues are encountered in the addition of antisolvents and reagents for reactive crystallization because nucleation is a function of supersaturation, whether local or global. 

Although crystallization by antisolvent addition shares many characteristics with that caused by chemical reaction, the processes often differ in the rate of creation of supersaturation (e.g., a rapid reaction leading to a compound of very low solubihty). Reactive crystallization is also subject to other kinetic considerations which are sometimes less predictable than the known solubility effects caused by addition of an antisolvent. 

Classification of batch crystallizers and batch crystallization operations according to the means by which supersaturation is created is still a widely accepted method. Therefore, the discussion of such operations may include cooling crystallization, evaporative crystallization, vacuum crystallization, antisolvent crystallization, reaction (reactive) crystallization, etc. The vacuum crystallization operation can be considered as a combination of the evaporative and cooling crystallization and thus will not be discussed separately. Reaction crystallization (precipitation) is discussed in detail in Chapter 6. 

The path of the antisolvent and reactive crystallization in the phase diagram is characterized by the mixing line. Mixing schemes will be discussed in Chapter 12. It should be noted that an antisolvent or a pH shift crystallization can be run... 

For an evaporative crystallization, inhomogeneties exist in the boiling zone and at the solution/bubble interface. Finally, for an antisolvent or reactive crystallization, the macro- and micromixing in the zone of addition can lead to substantial inhomogeneties. 

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