(543h) Optimizing Carbon Treatment Methods for Successful Scale-up

Carbon treatment is a technique used to remove polymer, metals, and other impurities from pharmaceutical process streams to improve the purity of isolated products. Activated carbon, used in this unit operation, is porous with high surface area that can selectively adsorb impurities to it. This adsorption capability is influenced by the origin of the activated carbon and its method of activation among other operational factors. In this work, we investigate the impact of operational factor influences on the adsorption selectivity for several process streams for a given type of activated carbon.

The synthesis route of Belzutifan consists of several reaction steps that generate polymeric impurities. These species affect the crystallization performance as well as the purity of the intermediates and the active pharmaceutical ingredient (API). Carbon treatment prior to the crystallization of the intermediates and the API normalizes the streams to ensure process robustness. While optimizing the carbon loading in the process, we observed the relationship between operational factors and carbon treatment performance.

In this work, we focus on two such factors, first is the use of loose activated carbon particles versus carbon cartridges. Second, we investigate the method of operation of the carbon cartridges with regards to flowing process streams through them single pass versus recycled. Since adsorption properties are influenced by the nature of the molecules being adsorbed (MW, functional groups etc.), this study explores process streams with different analytes and solvents to understand if results are translatable across them. Based on early findings, we have seen that the loose activated carbon shows differences in the efficiency of polymer purge compared to carbon cartridges despite using the same wt% ratio of carbon to the starting material. Further, there are differences in impurity purge when using carbon cartridges in a single pass versus a recycled configuration that depend on the number of turnovers used. The goal of this project is to provide a best practices guideline for future use of carbon treatment in projects to ensure that researchers do not see varied results when operating in different configurations.