(138a) Development of an Adsorbent Treatment Workflow for Impurity Removal

Critical Quality Attributes (CQAs) of a small molecule drug substance, such as chemical purity and physical properties, are often correlated due to the impact of impurities on both crystal morphology and crystallization kinetics.¹ Addressing the CQAs with a robust crystallization process can be difficult when impurities cause liquid-liquid phase separation (oiling) during crystallization.² Adsorbent treatments such as functionalized silica or activated carbon can be used to purify process streams and reduce the occurrence of oiling during crystallization.^3-5 For this case study involving a small molecule drug substance, an adsorbent treatment workflow was developed to determine when an adsorbent treatment is needed and to facilitate process design. Key design parameters investigated include temperature, solvent system, adsorbent type, and adsorbent loading. A partial least squares (PLS) regression model was developed to evaluate the data, and a database was created for future projects to enable rapid statistical analysis and to correlate absorption performance (e.g., selectivity, yield) to drug substance chemical purity and physical properties.

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5. Welch, C. J., Albaneze-Walker, J., Leonard, W. R., Biba, M., DaSilva, J., Henderson, D., ... & Wang, T. (2005). Adsorbent screening for metal impurity removal in pharmaceutical process research. Organic process research & development, 9(2), 198-205.