Introduction to Crystallization and Precipitation

Crystallization touches every aspect of our lives from the foods we eat and the medicines we take, to the fuels we use to power our communities. The majority of pharmaceutical products go through at least one crystallization step during their manufacture.  Salt and sugar are delivered to our dinner tables as crystals.  The unwanted crystallization of gas hydrates played a role in the recent Deepwater Horizon oil spill.

crystallization introductionScientists and engineers working in many industries around the world are required to understand, optimize and control crystallization processes every day. The purpose of this series of blog posts is to introduce key crystallization concepts from the ground up and highlight the many resources available for those working in this exciting field.

We can start with a few definitions:

  • Crystallization: A process whereby solid crystals are formed from another phase, typically a liquid solution or melt.
  • Crystal: Solid particles in which the constituent molecules, atoms or ions are arranged in some fixed and rigid repeating three-dimensional pattern or lattice.
  • Precipitation: It is a little bit difficult to define the term precipitation. For some, it is simply a fast, perhaps uncontrolled, crystallization process. For others, it is crystal formation resulting from a chemical reaction. It can also vary by industry; in the pharmaceutical industry, “crystallization” is common and in the chemical industry “precipitation” is the vernacular. For the purpose of this blog, the two will be used interchangeably.

The prevalence of crystallization processes in industry can probably be attributed to the fact that crystallization acts as both a separation and purification step. In one fell swoop, crystal product of the desired purity can be created and then isolated. Despite this obvious advantage, crystallization processes still need to be understood and controlled to ensure the desired crystal product quality is achieved and to ensure an efficient and cost-effective crystallization process.

The reference below summarizes this nicely by highlighting the importance of ensuring product and process quality.

Product Performance

“Crystallization of an API [active pharmaceutical ingredient – the crystal product] in particular is critical for product qualities such as chemical purity and correct polymorphic form, which need to be strictly controlled to meet set specifications.”

Process Performance

“The API crystallization process and crystal properties have a significant effect on downstream processing. For example, excess fines or wide particle size distribution may cause slow filtration and inefficient drying, which may be a major bottleneck of the entire manufacturing process1”.

In the next blog post in this series, we will introduce some different ways to drive a crystallization process as well as establish the foundation for crystallization process design, solubility.

1.       Kim S. et al., “Control of the Particle Properties of a Drug Substance by Crystallization Engineering and the Effect on Drug Product Formulation” Organic Process Research & Development, 9, 894-901 (2005)

If you are interested in discussions with others working and interested in crystallization, consider joining the 600+ member LinkedIn Crystallization Community.