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.
Cobalt Light Systems Ltd, 174 Brook Drive, Milton Park, Abingdon, Oxfordshire, OX14 4SD, UK.
Julia
J
Griffen
Cobalt Light Systems Ltd, 174 Brook Drive, Milton Park, Abingdon, Oxfordshire, OX14 4SD, UK. Electronic address: Andrew.Owen@cobaltlight.com.
Andrew
A
Owen
Cobalt Light Systems Ltd, 174 Brook Drive, Milton Park, Abingdon, Oxfordshire, OX14 4SD, UK; Central Laser Facility, Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Harwell Oxford, OX11 0QX, UK.
Pavel
P
Matousek
D000082:Acetaminophen / Q000032:analysis*; D002110:Caffeine / Q000032:analysis*; D002138:Calibration; D005079:Excipients / Q000032:analysis*; D016018:Least-Squares Analysis; D008962:Models, Theoretical; D015999:Multivariate Analysis; D010656:Phenylephrine / Q000032:analysis*; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013607:Tablets
D005079:Excipients; D013607:Tablets; D010656:Phenylephrine; D000082:Acetaminophen; D002110:Caffeine
Pharmaceutical formulations; Quality control; Quantitative analysis; Transmission Raman spectroscopy