Development of a Spatially Resolved Spectroscopy probe for In-line Monitoring of Pharmaceutical Drying

Description:
Pharmaceutical manufacturing is experiencing rapid changes with substantial requirements to improve process understanding and quality control. It has driven the emergence of Process Analytical Technology (PAT), which analyze critical quality attributes of pharmaceuticals in-situ and in real-time, to replace conventional laboratory-based approaches. Near-infrared (NIR) and Raman spectroscopies are vibrational techniques spearheading the adoption of PAT in the sector. Drying is a complex and inherently non-uniform process that relies on the transfer of heat to the product to evaporate the solvent, the diffusion of the solvent from within the product, and its transfer out of the dryer. Applying conventional, single-point Raman and NIR measurements to monitor drying process encounters limitations due to the techniques being developed for measurement from/near the surface of a uniform system. To overcome this challenge, we developed an integrated in-line PAT solution that uses spatially resolved spectroscopy (SRS) to collect the complementary Raman and NIR spectra and analyse sub-surface chemical and physical information.

The study uses paracetamol and various drying solvents as the model system, and SRS spectra are analyzed using multivariate regression modeling. Compared to conventional Raman and NIR measurements, the SRS probe observes solvent signals from a subsurface deeper than 10 mm, with the potential to reach a deeper layer by further increasing the spatial distances. When applied to monitor the drying process, the regression models suggest that the SRS probe provides improved performance in estimating solvent content, a critical quality attribute of the final product. The result shows that the signals collected from offsets provide reduced errors by around 50% in the prediction of the solvent content. This study supports the potential of using SRS for in-line monitoring of complex processes and product where uniformity is crucial or difficult to control.

Speaker: Yi-chieh Chen - University of Strathclyde, Department of Chemical Enginering
Dr. Yi-chieh (Claudia) Chen is currently a senior lecturer in the Department of Chemical and Process Engineering at the University of Strathclyde. She has 20 years’ experience working in advanced spectroscopy and its applications in various research and industry sectors.

Claudia's research focuses on developing novel measurement-interpretation platform for advanced manufacturing and process development. She is one of the inventors of the innovative SAR-DRM system and received the prestigious Converge Challenge 2014 Award in recognition of the business potential of the system. Her long term goal is to lead integration of analytical science to reduce the gap between instrument innovation and its applications. Claudia leads the Measurement and Analytics Team in Strathclyde and provides an industrial-oriented research environment to facilitate prospective partners and researchers, nurturing novel ideas to deliver impacts on chemical process sector.