Quantifying low levels (<0.5% w/w) of warfarin sodium salts in oral solid dose forms using Transmission Raman spectroscopy

Abstract

In this feasibility study Transmission Raman spectroscopy (TRS) has been used to build quantitative models for warfarin sodium and warfarin sodium clathrate. The type of warfarin present in manufactured tablets may affect product quality. Models were used to predict warfarin sodium in commercially available tablets at extremely low dosage levels (0.5% w/w). The laboratory made calibration samples used in the modelling varied in amorphous sodium, crystalline clathrate warfarin forms, excipients and dye. This application was highly challenging due to the low level of API and high level of a Raman-active colourant which varied significantly between production batches. A photon recycling optic, known as a Beam Enhancer, was utilised to improve the signal to noise of the Raman spectra to attain a low limit of quantification of 0.19% w/w.

Keywords: Crystallinity; Polymorphism; Raman spectroscopy; Transmission Raman; Warfarin.