This is the fifth blog post in a series dedicated to crystallization. In case you missed the previous posts in the series, they are available here:
- Introduction to Crystallization and Precipitation
- Common Ways to Reduce Solubility and Drive Crystallization
- Supersaturation: Driving Force For Crystal Nucleation & Growth
- Importance of Crystal Size and Shape Distribution
The diagram below illustrates the relationship between supersaturation and crystal size distribution, via crystal nucleation and growth. In this post, we will look at how supersaturation can be controlled by adjusting process parameters such as antisolvent addition rate. In the next post, we will delve a little deeper into the fundamentals of crystallization kinetics – but for now we will investigate an interesting case study where in situ monitoring tools are used to monitor supersaturation and track the subsequent impact on crystal size distribution.
This example looks at the impact of antisolvent addition rate on crystal product size, morphology and population for the unseeded crystallization of benzoic acid from ethanol-water mixtures. Using water as the antisolvent two experiments were conducted at a slow (0.1g/s) and fast (0.2g/s) antisolvent addition rate. Supersaturation was monitored using ReactIR, particle count and dimension was characterized using FBRM and the size and shape of the crystals was assessed using PVM.
Undersaturated solutions of benzoic acid in aqueous ethanol solutions were prepared and held at a constant temperature of 25ºC. Benzoic acid is an organic compound, poorly soluble in water but soluble in ethanol with no known polymorphs cited in the literature. Water was added at a fixed rate of 0.1 g/s and 0.2 g/s respectively and the resulting crystallization was monitored using in-situ process analytical tools.
Figure 1 shows the solubility curve for benzoic acid in ethanol-water mixtures with desupersaturation profiles overlaid for each experiment. The desupersaturation profile shows that the solution begins in the undersaturated region and as water is added moves past the solubility curve into the supersaturated region. The liquid concentration decreases upon crystal nucleation, stays close to the solubility curve, and at the end of the antisolvent addition period drops to the solubility curve. The prevailing level of supersaturation is clearly seen in Figure 2 where anti-solvent concentration vs. supersaturation is displayed.
Evidently, at the faster addition rate, supersaturation is higher – a critical result! In general, a fast cooling or addition rate results in high supersaturation levels. This is because the kinetics of crystal nucleation and growth are typically not fast enough to consume the supersaturation immediately, allowing it to build up as the crystallization progresses.
We know from previous sections that high levels of supersaturation can often lead to a nucleation-dominated crystallization with little crystal growth. Figure 3 shows FBRM distributions at the end of each experiment – clearly the fast addition rate exhibits a much higher population of small crystals, whereas the slow addition rate exhibits a larger particle dimension.
It is not simply crystal size that is influenced by changing process parameters – crystal shape is also influenced. PVM images taken at the end of each experiment illustrate this with the slow addition rate yielding large, well-formed elongated plates. While the fast addition rate yields fine needles that readily, agglomerate.
The case study above illustrates how changing process parameters can directly influence the prevailing level of supersaturation and the subsequent crystal size, population and shape.
In the next post in this series, we will delve a little further into the fundamentals of crystallization kinetics. In the meantime this webinar and paper may prove interesting:
M. Barrett, M. McNamara, H. Hao, P. Barrett, and B. Glennon, “Supersaturation tracking for the development, optimization and control of crystallization processes,” Chemical Engineering Research and Design, vol. 88, Aug. 2010, pp. 1108-1119.
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