Raman Imaging Gallery - Single Point Analysis and Raman Mapping of Tablet Dosage Formulation as a Means for Detecting and Sourcing Counterfeit Pharmaceuticals
Mark Witkowski and Dr Fran Adar
US Food and Drug Administration’s Forensic Center, Cincinnati, OH, USA
HORIBA Jobin Yvon Inc., Edison, NJ, USA
The development of methods to rapidly differentiate counterfeit pharmaceuticals from authentic products is one of the ways to prevent these products from entering the drug distribution chain. The capability of vibrational spectroscopy to identify the molecular and crystalline phase of almost any material has been exploited to characterize suspected counterfeit pharmaceutical tablets by combining spectroscopy with spatial mapping and multivariate analysis of Raman maps. Single point Raman and FTIR spectra, and maps of authentic and counterfeit tablets effectively demonstrate which seized suspect products are counterfeit that could not come from legitimate manufacturers, a conclusion derived from the identification of the excipients and from their distribution. This work has added importance because samples are not destroyed before or during analysis, making them available for further investigations.
Figure 1: Loadings of the API and 3 excipients extracted by Multivariate Analysis.
Confocal XY maps were recorded from freshly cleaved surfaces. Because of the complexity of the spectra there is almost always spectral overlap. Multivariate techniques, especially Factor Analysis with Alternating Least Squares, Score Segregation and Binary Rotation, enable one to spatially isolate contributions from the different species. The high spatial resolution of the Raman technique also makes it easy to detect the presence of materials such as Mg stearate that are present at low levels.
Results from the suspect tablets are shown. The first figure shows the "purified" loadings generated through IsysTM, data is easily passed between LabSpec and IsysTM, in both directions, using direct icon selected links. These loading spectra are then used by the modelling function in LabSpec to create the multicolored image in the second figure. Note that all all the particles in this figure are 20 µm or greater.
Figure 2:Raman image created by the modeling function in LabSpec, using the factor loadings derived by Isys™.
This image shows large amounts of starch (not present at all in the authentic tablet) and large amounts of lactose (more than what was observed in the authentic sample). Products of the innovator companies are consistently well dispersed in the manufacturing process, which is not always the case with counterfeit products and Raman mapping is one method which allows for the excipient particle size and dispersion to be assessed. In this example Mg stearate, a component that is present at low concentrations was detected and this can be quite important because Mg stearate is added as a lubricant, but can inhibit bioavailability of the API if it encapsulates the API or dispersants.
These results are part of an ongoing collaboration between HORIBA and Mark Witkowski at the US Food and Drug Administration's Forensic Chemistry Center in Cincinnati, Ohio.
The mentioning of specific products / instruments in this presentation is for information purposes only and does not constitute an endorsement by either the Food and Drug Administration and / or the Forensic Chemistry Center.
