Application of Ultra-Performance Liquid Chromatography as an Online Process Analytical Technology Tool in Pharmaceutical Crystallization

Abstract

Concentration is often an important process parameter in pharmaceutical crystallization processes. In this work, an ultra-performance liquid chromatography (UPLC) system designed for process monitoring (Waters PATROL UPLC) was applied online as a process analytical technology tool for real-time multicomponent concentration monitoring in pharmaceutical crystallization. Three online UPLC-based applications were investigated: (1) solute concentration monitoring during crystallizations and associated solubility, dissolution, and degradation analyses, (2) quick calibration for UV/vis and Raman spectroscopy, and (3) real-time crystallization product purity monitoring.