Comprehensive quantification of tablets with multiple active pharmaceutical ingredients using transmission Raman spectroscopy--a proof of concept study.

Transmission Raman spectroscopy is a potent new tool for content uniformity testing in pharmaceutical manufacturing enabling rapid bulk sampling of a material by non-destructive means. In this proof-of-concept study, we present, for the first time, comprehensive quantification of all the constituents in a set of tablets consisting of 5 components (3 APIs and 2 excipients) by this method. The nominal concentration of individual components ranged from 1 to 85% (w/w). Two multivariate partial least-squares approaches have been used to calibrate concentration models consisting of 40 handmade tablets covering 20 sample points. These models successfully predicted all the components in a set of 10 validation tablets covering 5 different sample points. A single model for all components (PLS2) and 5 individual models each optimised for one component (PLS1) performed similarity and have been used to demonstrate that specificity of prediction has been achieved through using a multifactor orthogonal DoE for sample preparation. The ability to determine multiple analyte concentrations in one single measurement further establishes this procedure and its benefits for assay and content uniformity testing.