Unseeded crystallization

Primary nucleation is the classical form of nucleation. It occurs mainly at high levels of supersaturation and is thus most prevalent during unseeded crystallization or precipitation. This mode of nucleation may be subdivided into either homogeneous viz. spontaneously from clear solution, or heterogeneous viz. in the presence of dust particles in suspension, or solid surfaces. 

Figure 11.9 shows the process paths for different cases and operating conditions. This base case examines an unseeded crystallization without racemization reaction. 

Carsten Jacobsen (Novo Nordisk) presented results on protein crystallization in preclarified, concentrated fermentation broths. In particular, the impact of filtration rate on the formation of favorable large diamond versus rod shapes was examined. By adding seed crystals just above the solubility curve, where no nucleation occurred, the authors were able to produce 30% larger crystals as compared to an unseeded crystallization. Although there was minimal recovery and characterization data, this technique may prove very beneficial for dealing with difficult feed streams. While the work presented in this talk was done at the laboratory scale, scale-up experiments will be required to confirm the suitability of this approach for industrial process applications. 

Fig. 13 Optimal temperature profile calculated from a first-principle model for maximizing the mean crystal size for unseeded crystallization of paracetamol in water and the simulated change in mean crystal size during crystallization.

Figure 2. Diagram of furnace used for unseeded crystal growth by slow cooling of high temperature solutions. (From Ref. 5.)...

Figure 10.18 Cooling profiles for crystallization of MgSO4 -7H20 in a 21-L batch cooling crystallizer, as reported by Karpinski et al. (1980b). Saturation temperature T = 35 °C. Seeded crystallization (1) Cooling profile calculated from Eq. (10.54), mean seed size i, = 0.4075 mm. Unseeded crystallization (2) Cooling profile calculated from Eq. (10.56), (3) Linear cooling profile, (4) Natural cooling profile.

Batch Crystallization. Crystal size distributions obtained from batch crystallizers are affected by the mode used to generate supersaturation and the rate at which supersaturation is generated. For example, in a cooling mode there are several avenues that can be followed in reducing the temperature of the batch system, and the same can be said for the generation of supersaturation by evaporation or by addition of a nonsolvent or precipitant. The complexity of a batch operation can be ihustrated by considering the summaries of seeded and unseeded operations shown in Figure 19. 

Carefully selected seed crystals are sometimes added to a crystalliser to control the final product crystal size. The rapid cooling of an unseeded solution is shown in Figure 15.20a in which the solution cools at constant concentration until the limit of the metastable zone is reached, where nucleation occurs. The temperature increases slightly due to the release of latent heat of crystallisation, but on cooling more nucleation occurs. The temperature and concentration subsequently fall and, in such a process, nucleation and growth cannot... 

An experiment was performed to examine the supposition that increases in supersaturation lead to greater impurity content in crystals. In a batch unseeded cooling crystallizer supersaturation is expected to be high at the point of nucleation, diminish rapidly after nucleation and then approach zero as the batch is... 

Figure 4. Correlation between relative supersaturated pressure and crystallization rate (unseeded, 283 K)...

Synthesis of Zeolite A. Zeolite A was crystallized from a batch of overall composition 2.5 Na20-Al203-1.7 SiO2-150 H20 at 60, 75, and 90°C (10). The same system was seeded with zeolite A crystals of 0.5-5 /zmeter size at an initial conversion level of 25% and crystallized at 60°C. As with the crystallization of zeolite X from seeded systems, the data were treated by ignoring the presence of seed crystals. The crystallization curves are shown in Figure 8. During the induction time period in the unseeded system, crystallization was taking place at a slow rate in the seeded system, both at 60°C. After this slow crystallization period the crystallization rate reached 22% per hour at the 50% conversion level... 

This study showed that the overall crystallization processes for mor-denite, zeolite X, and zeolite A were similar. However, the physical properties of the crystallizing system determine the rate-limiting step for a particular zeolite synthesis. In the case of mordenite in which both the viscosity of the batch composition and the morphology of seed crystals were varied, it was observed that diffusion in the liquid phase was the ratedetermining step. For zeolite X the actual growth rate on the crystal-liquid interface was the rate-limiting factor as shown by identical conversion rates for the seeded and unseeded systems. For zeolite A in the system chosen, both processes influenced the conversion rate. 

It was possible for two of the systems chosen that the nucleation and crystallization activation energies could be determined separately by distinguishing the induction period and crystal growth period in the overall crystallization process. Of the two hypotheses proposed for zeolite crystallization, in the gel phase or from the solution phase, the data support the latter hypothesis for crystal growth with the crystal-liquid surface enhancing the nucleation process in seeded systems. The precise mechanism of nucleation in unseeded systems remains to be determined. 

In Fig. 6, point P represents a solution that is unsaturated at this concentration neither nucleation nor crystal growth will occur. Point S represents a labile solution which will nucleate spontaneously, with concentration falling to point R as nucleation and crystal growth occur. Point Q represents a metastable concentration at which growth will take place if crystal seeds are present or added. Although the supersolubility limit is affected by external factors, discussed later, the Miers concept is useful as an empirical representation of nucleation behavior and in treating crystallization from unseeded solutions. 

Pertinent to this discussion of spontaneously seeded batch operations is an investigation by Schlichtkrull (S8) in which the seeded and unseeded cases are compared. In these experiments with insulin crystals,... 

Excellent control of crystaUization conditions can be achieved by semicontinuous methods in which the supersaturation is controUed locaUy at the point of mixing in an in-line device. Both once-through and recycle operations can be carried out with and without seeding. In the case of unseeded operation, an in-line device can create a high supersaturation ratio in a very short time and provide a method of control of nucleation that is difficult or impossible to achieve in conventional crystallization vessels. 

The initial population density n L, 0) for a batch crystallizer is not well defined. For a crystallizer seeded externally, n(L, 0) may be denoted by an initial seed distribution function hs L). However, in an unseeded system, initial nucleation can occur by several mechanisms, and one cannot realistically use a zero initial condition for the size distribution. To overcome this difficulty, Baliga (1970) suggested the use of the size distribution of crystals in suspension at the time of the first appearance of crystals as the initial population density. 

One of the main challenges in batch crystallization is to control the supersaturation and nucleation during the initial stage of the batch run. During this period, very little crystal suspension is present on which solute can crystallize, so that high supersaturation and excessive nucleation often occur. Another difficulty associated with batch crystallization is the determination of the initial condition for the population density function. In an unseeded batch crystallizer, initial nucleation can occur by several mechanisms and usually occurs as an initial shower followed by a reduced nucleation rate. Thus, an initial size distribution exists and one... 

Unseeded Cooling Crystallization. In a similar fashion, a cooling profile can be derived for the unseeded case in which spontaneous nucleation and growth are allowed to occur at constant rates. The actual solutions to the resultant third-order differential equations found in the literature differ due to the different sets of the four initial conditions used by various authors (Karpinski et al. 1980b Nyvlt 1991 Randolph and Larson 1988). Understandably, all of them result in a cooling profile of the general form... 

Based on the two cases discussed so far, one can consider yet another case of interest, in which nucleation is allowed to proceed at a constant rate from t = 0 until a certain time /], after which no new nuclei are generated. For sueh a cooling crystallization, a biquadratic cooling profile applies until t = t, and Eq. (10.54) for the time t> t. This is the preferred method of praetical unseeded batch cooling crystallization. 

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