Crystallization is easy! You just cool the solution and out drops your product. That’s a delusion as numerous plants can attest. Many products that start out in this manner cause problems in downstream processing. For instance, fine crystals may not separate from the solvent completely and drying may take a long time.
Once the chemists have given you a process — react, cool, separate and dry — they should look at various scenarios and alternative routes to the product. Such alternatives certainly exist. Cooling may not be the optimum way to generate supersaturation.
So, let’s examine five alternative routes that you should suggest to the chemists:
1. Generate enough supersaturation to nucleate the product and slowly grow the crystals to a large size. Sometimes this means an incubation period or even a fines-destruction step to ensure the correct number of nuclei. The crystals should be big enough to separate from the solvent easily and even to allow their washing. With less solvent to evaporate, drying can be more rapid. Often, the equipment required for the downstream processing is less expensive and smaller. Generally, this is a big benefit. However, spending a lot of time in the crystallization process to make a large particle can destroy that advantage.
2. Generate the supersaturation and introduce seeds or artificial nucleation via sonication to control the number of nuclei. This extra step may make the solvent easier to remove, even with a smaller crystal. This results in less time spent crystallizing while still realizing a reduced drying time.
3. Remove the excess nuclei generated by primary or secondary nucleation via fines destruction, and return that solute to the crystallizer. This will allow operating at a higher supersaturation that will increase growth rate, reduce crystallization time, and maintain the advantages cited in the first route. An optional way to remove excess fines is through Ostwald ripening, where the batch is held at the end of crystallization to re-dissolve fine particles onto larger crystals.
4. Rather than making a large crystal, stick with the fine product and perform multiple crystallizations using the solvent in a cascade manner to wash the crystals or even use liquid/liquid extraction to purify the wash. The fine particles produced can be agglomerated during drying or pelletized through extrusion to give granular product of the desired size.
5. Remove solvent instead of cooling. While cooling works well for many chemicals, some have unusual, if not strange, solubility curves. In such cases, you must remove solvent to generate supersaturation. Also, polymorphs can complicate the crystallization, especially if the solubility curves cross at some temperature. Solvent evaporation often makes more sense than cooling when considering options such as fines destruction. Addition of anti-solvents also may outperform other means of generating supersaturation.
You should evaluate, at least on paper, all these routes before selecting a process design or type of crystallizer.
Many process designs run into problems when the meta-stable-zone width isn’t well defined or understood. Indeed, I’ve seen numerous difficulties occur because of this oversight. You should generate solubility curves both from solution and dissolution of the product to determine this no-man’s land of solubility. Such curves will help any manufacturer of crystallizers make the best suggestion for a device. Also, this information will ease grappling with future process or quality problems.
The most overlooked physical properties in a crystallization process are growth and nucleation rate. Growth often is expressed as time to reach an average size and never has been studied as a function of supersaturation and particle size. I realize that both nucleation and growth aren’t easy to understand, but an analysis of the particle size distribution gives a starting point to estimate growth and evaluate other routes that might provide a better and cheaper product.
The alternatives suggested above don’t address one of the most critical choices made in the process design: whether to opt for batch or continuous crystallization. Plants often make this choice based on upstream or downstream operations along with what equipment is available or has been used in the past. However, sometimes changing upstream/downstream operations can lead to an overall process that provides optimum quality and cost.
TOM BLACKWOOD is a Chemical Processing Contributing Editor. You can email him at TBlackwood@putman.net.