Reactive crystallization acid base in the API industry, involving organic acid with an inorganic base (NaOH), both solids in ethyl acetate solvent in the last step in order to obtain a final product before the solid treatment.
The reaction that generated the impurity was the hydrolysis of the solvent with the base. As a result of this impurity, the final product was out of specifications.
Failures during scale-up. An additional problem arose when we shifted the processes to a second system (at the same scale), resulting in an approximately three-fold rise in impurity.
Eliminate the rise in impurity during scale-up
The Traditional Approach
Try to achieve better homogeneity of solid distribution in the new system.
The VisiMix Analysis
Surprisingly, the radial distribution of solids in the reactor, where the purity was acceptable, was less homogeneous than it was in the unsuccessful reactor. VisiMix analysis found that the fast reaction was between the solvent and the base, and when homogeneity is higher there is a rise in impurity.
The VisiMix Solution
After multiple simulation scenarios, it was proven that it is not possible to reach acceptable conditions in the scale-up system and maintain the required impurity level of the product. To achieve satisfactory results the NaOH needed to be added as a solution.
Scale-up by a factor of 4 succeeded and achieved a four-fold increase in productivity, a gain estimated at more than $2,000,000 per year.
VisiMix helped identify and implement a new way of thinking about improving the continuous process in the production step. Since then, every time we begin a new process we first evaluate the VisiMix results.