MULTICOMPONENT CHEMICAL IMAGING OF PHARMACEUTICAL SOLID DOSAGE FORMS WITH BROADBAND CARS MICROSCOPY

 

Christopher M. Hartshorn, Young Jong Lee, John Heddleston, Charles H. Camp Jr., Patrick J. Marsac, and Marcus T. Cicerone

 

Development of Process Analytical Technologies (PAT) for the pharmaceutical industry requires specialized analytical tools that can successfully measure Critical Process Parameters (CPPs) rapidly and accurately. We report here the quantitative and qualitative assessment of multicomponent pharmaceuticals utilizing broadband coherent anti-Stokes Raman scattering (B-CARS) microscopy at very low acquisition times (<100ms/pixel dwell times). The active pharmaceutical ingredient (API) indomethacin, a non-steroidal anti-inflammatory drug, was used in its final dosage form (e.g. tabulated) embedded within powdered excipients as to represent a real world process-monitoring scenario. In order to validate the chemosensitive nature of B-CARS, mixtures of Indomethacin γ/α-polymorphs were also formulated and imaged. B-CARS microscopy efficiently delineated both polymorphs in tablets and with high spatiochemical resolution (800-3400cm-1 spectral windows in 1 m steps). In order to validate the rapid imaging potential of B-CARS, several similar techniques were performed as a comparison. B-CARS improved upon image acquisition times of confocal spontaneous Raman microscopy by 100x and eliminated the need for processing steps (e.g. multivariate methods) with comparable spatiochemical sensitivity and improved upon acquisition times of a wide-field chemical imaging microscope by 10x with much higher spatiochemical resolution than this technique can offer .