Development of spatially resolved spectroscopy for in-situ, real-time monitoring of pharmaceutical isolation process

Pharmaceutical drug isolation is a critical process which involves steps such as filtration, washing and drying to connect the upstream (synthesis and crystallisation) and downstream (formulation and tabletting) processes. The isolation processes are complex due to the heterogeneous nature of the content involved. Many issues, such as particle dissolution and residual crystallisation solvent in washing or agglomeration formation in drying, are difficult to measure or link with the process conditions for off-line analysis. It is highly desired to collect real-time data throughout the process; however, this is prohibited by limitations of existing process analytical technology (PAT) tools to simultaneously measure the full contents in the unit. Spatially resolved spectroscopy (SRS) is developed for the two most widely studied PAT techniques, Raman and near-infrared (NIR) spectroscopy, to obtain subsurface chemical and physical information. This is achieved by collecting returning Raman and NIR photons which penetrate deep into the system and being scattered by the particle and agglomerates inside the system. This approach effectively increases the sampling area of a system for more representative analysis and can provide the profile of the system by analysing the differentiable signal corresponding to different depths. The project plan to identify opportunities and limitations enabled by the in-line SRS probe to systematically understand different stages of isolation processes.

The project has three major objectives:

• Establish the performance matrix of SRS technique (for both Raman and NIR measurements) in determining residual crystallisation solvent and dissolution of particles in filtration and washing processes;

• Determine the physical and optical design of the probe and its coupling to batch filtration/washing units, and the recently developed continuous filtration unit;

• Integrate the information obtained from analysing the filtration/washing unit and those from the DryingPAT project to identify strategies and design for an integrated continuous isolation unit. 

In addition to undertaking cutting edge research, students are also registered for the Postgraduate Certificate in Researcher Development (PGCert), which is a supplementary qualification that develops a student’s skills, networks and career prospects.

Information about the host department can be found by visiting:

www.strath.ac.uk/engineering/chemicalprocessengineering

www.strath.ac.uk/courses/research/chemicalprocessengineering/