In the relentless pursuit of optimizing pharmaceutical production, Sanofi’s Manufacturing Sciences, Analytics and Technology (MSAT) department has turned its gaze towards an often overlooked yet critical process: precipitation. This process, which involves the separation of a desired product from a solution, can significantly impact the final product’s physical and chemical characteristics. Julian Lopez, a key figure in Sanofi’s MSAT department, has been at the forefront of this investigation, recently publishing his findings in the ‘MATEC Web of Conferences’ under the title “Online monitoring of a precipitation step on small-scale equipment by conductivity and mathematical modeling.”
The research focuses on a specific precipitation step in Sanofi’s production line, where a non-solvent is added to a stirred tank in a semi-batch process. The mechanism behind this process is fascinating: it relies on electrostatic interactions between a cation from a salt in the mixture and a negatively charged polyoside, the product of interest. As the non-solvent is added, it alters the solubility of the mixture, causing the polyoside to form an unstable complex that aggregates and settles, allowing for phase separation.
To delve deeper into this process, Lopez and his team constructed a scaled-down 2-liter model of the production setup. They integrated electrical conductivity and temperature probes to monitor the system’s dynamics in real-time. “The non-solvent doesn’t release ions, so as it’s added, the ionic concentration in the mixture decreases, and so does the conductivity,” Lopez explains. This decrease in conductivity served as a proxy for tracking the progress of the precipitation reaction.
The team then developed a mathematical model using the Avrami (or JMAK) kinetic model to identify key parameters, such as the rate constant (k) and the Avrami exponent (n). Their findings revealed that the precipitation process follows first-order kinetics, regardless of the specific conditions tested. Moreover, while temperature didn’t seem to affect the phase transformation, the flow rate of the non-solvent had a direct, linear correlation with the precipitation rate.
This research has significant implications for the pharmaceutical industry and beyond. By understanding and controlling the precipitation process, manufacturers can improve product consistency and yield, ultimately leading to cost savings and enhanced efficiency. Lopez’s work also opens avenues for further exploration, such as applying this approach to other unit operations or integrating it with advanced process control strategies.
As Lopez puts it, “Our goal is to leverage this understanding to develop more robust and efficient processes, ultimately benefiting both our operations and the patients who rely on our products.” The insights gained from this research could pave the way for more precise and efficient manufacturing processes, not just in pharmaceuticals, but in any industry where precipitation plays a crucial role.
