Supersaturation: The Multiverse of Innovation for Solid Formulations

When I started this newsletter I’ve chosen a boring name for describe the supersaturation: It supposed to be: Typical ways to access the supersaturation solution. But this title is far from the grandiosity of this area in the crystallization process. So, I decided to change this title and I hope you can see from the same perspective as I do and agree with the grandiosity behind Supersaturation.

The supersaturation condition for a liquid solution is when there is an excess of solute to solvent, or the number of molecules solvated are lower than the required for the temperature and pressure to form a solution. And if you are keeping your reading in day, you will remember that I have said that the only path for nucleation and growth is from a saturated solution.

Some of you must have intimacy with the conditions that can lead to a supersaturated solution, like cooling, anti-solvent, solvent evaporation, and chemical reaction. So if the nucleation and growth come from a supersaturated solution, and if controlling the nucleation and growth is the point for obtaining the critical quality as well critical process parameters desired, to improve for example the bioavailability as well the flowability in the downstream process, we can understand how important is the control of the supersaturation solution.

And for this there are tools that can improve this fine control. To analyze the system conditions #PAT (process analytical technology) has been successfully used. In 2004 FDA published a guide for industries concerning in situ technologies used for efficient manufacturing. From Lawrence X. and coworkers paper (Applications of process analytical technology to crystallization processes) also from 2004, they describe PAT as systems for design, analysis. and control of manufacturing process. Been used for raw materials, in-process materials, and final products.

Probes wich uses attenuated total reflectance (ATR) technology are good examples of instrumentation useful for the crystallization process, they allow the measurement of liquid phase concentration despite the presence of solid particles. We can cite ATR-FTIR spectroscopy and ATR-UV/Vis. We can also for this propose use Raman spectroscopy. In this sense, we can cite instrumentation companies selling ATR technologies as well Raman probes, like Tornado - A Bruker Company , BlazeMetrics and SPECTRAL SOLUTIONS . Using these probes is possible to analyze the saturation point and from this take actions to obtain the desired product.

?But the best still for come, the combination of the ATR probes or other in situ instrumentation, like dynamic image analysis with #AI, can help with predictive control as well modeling. For example in the paper from Ryan Leening and coworkers published this year (2023), entitled: Development of a Digital Twin for the Prediction and Control of Supersaturation during Batch Cooling Crystallization, you can have a very good example of the use of AI for control the supersaturation and obtain desired solid state attributes.

The digital twins are about to blow up the control of crystallization, and I hope you can understand from this article the grandiosity around supersaturation, my aim at the beginning of this paper, and how many innovations can be developed from a good understanding of this single point. Many companies are investing on the development of such technologies, like Pfizer, which financed the work from Yingzhe Zheng, Xiaonan Wang,* and Zhe Wu*, entitled Machine Learning Modeling and Predictive Control of the Batch Crystallization Process.

If you are interested in learn more about crystallization, and solid critical qualities attributes, you are invited to our course, which will happen first online and then in the beautiful city of Niterói, in NAB, just in front of Sugar Loaf, Rio de Janeiro Bay and Christ the Redeemer, next year (2023). Couldn’t have a better combination to discuss applied science, with excellent teachers and such a wonderful location. I dare you to find a better opportunity.

I hope you enjoy this paper, and for more information follow us on social media or contact us by e-mail: [email protected] or Whatsapp: +55 (11)978030087 or call +55(21)980087747.