Application of Mid-Infrared Spectroscopy to the Development and Transfer of a Manufacturing Process for an Active Pharmaceutical Ingredient

Abstract

The use of in situ mid-infrared spectroscopy to support the development of a pharmaceutical manufacturing process is disclosed. Data on this two-stage telescoped reaction from several reaction scales (<50 mL to 1600 liters) and at multiple manufacturing locations is shown. In addition to providing data on both reactions in the telescope, the mid-IR data has been used to monitor an intermediate distillation operation and therefore it has been possible to profile the whole process. Data is also shown on aliquot addition during the first chemical transformation, which is used to check the instrumentation.

Using PAT To Understand, Control, and Rapidly Scale Up the Production of a Hydrogenation Reaction and Isolation of Pharmaceutical Intermediate

“…In-line spectroscopy has been used extensively for monitoring of chemical reactions and crystallization processes from the laboratory through at least pilot-plant scale. − For hydrogenation reactions, the focus of recent examples in the literature has been on the use of mid-infrared (MIR) spectroscopy to gain a fundamental understanding of the process, to understand the effects of changing process conditions, or to determine the reaction kinetics. − However, there has been less focus on process control or real-time determination of the reaction end point. For distillation and crystallization processes, recent examples have included quantitative models using a range of spectroscopies to control solvent composition. , …”