Isolation of active pharmaceutical ingredients (APIs) is a critical process that links upstream (synthesis and crystallisation) and downstream (formulation and tabletting) operations, involving steps such as filtration, washing and drying. It is inherently complex and multiphase, as the process is driven by solvent mass transfer along a solvent-content gradient and involves heat transfer for solvent evaporation. Polymorphic transformations and solvation of solids can be induced by varying the thermal and solvent environment.

Spatially offset Raman spectroscopy (SORS) presents a promising opportunity to address this challenge. SORS employs a unique optical approach to increase the sampling depth and differentiate contributions from different depths. It shares the same fundamental principle as Raman scattering for sensing polymorphism and drug solvation/desolvation, and offers an advantage over existing process analytical technologies (PATs) by resolving Raman signals caused by local non-uniformity and sampling inside the bulk of the wet cake, delivering information critical for understanding the heterogeneous isolation process, such as solvent distribution and removal, and polymorph formation.

The team at Strathclyde has been developing SORS for pharmaceutical applications. The project will utilise our latest in-line SORS probe and the state-of-the-art facility for batch and continuous isolation units to gain insight of the complex isolation processes, linking local non-uniform conditions, such as the packed solid, local temperature differences, and solvent pockets, to the product's critical quality attributes.

Objectives

 The project has three major objectives:

• establish the performance and limitations of SORS in detecting local non-uniformity in solvent composition and distribution, solid desolvation, and polymorph transformation using a controllably formed model system
• determine the physical and optical design of the probe and its coupling to state-of-the-art continuous isolation units
• examine the SORS performance on wet cake prepared by isolation processes and connect it to the critical information on the conditions that promote polymorph transformation and desolvation

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.

Further information

Further information about the Chemical & Process Engineering department

Further information about the Chemical & Process Engineering PhD