Rapid quantification of low level polymorph content in a solid dose form using transmission Raman spectroscopy

Abstract

This proof of concept study demonstrates the application of transmission Raman spectroscopy (TRS) to the non-invasive and non-destructive quantification of low levels (0.62-1.32% w/w) of an active pharmaceutical ingredient's polymorphic forms in a pharmaceutical formulation. Partial least squares calibration models were validated with independent validation samples resulting in prediction RMSEP values of 0.03-0.05% w/w and a limit of detection of 0.1-0.2% w/w. The study further demonstrates the ability of TRS to quantify all tablet constituents in one single measurement. By analysis of degraded stability samples, sole transformation between polymorphic forms was observed while excipient levels remained constant. Additionally, a beam enhancer device was used to enhance laser coupling to the sample, which allowed comparable prediction performance at 60 times faster rates (0.2s) than in standard mode.

Spatially offset Raman spectroscopy

“…This process is exemplified by the quantification of pharmaceutical formulations using TRS in ReF. 84 .…”

Controlling phase transformation during milling in the pre-formulation of Active pharmaceutical Ingredients

“…Meanwhile, thermal analysis requires less amount of the sample 2-4 mg with longer detection time 20-30 minutes or more depend on the targeted process with easier detection of the polymorphic mixture [22]. Other characterization methods are: Raman spectroscopy [36] , polarized light microscopy [37] , FTIR [38] and many others.…”

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

“…TRS demonstrated a limit of detection (LOD) comparable with the ssNMR method (0.9% w/w) al be it with a measurement time of seconds and without the need to alter the sample in any way [21]. The most recent work demonstrated the capability of quantifying low (0.62 -1.32% w/w) levels of polymorph content, and additionally the sole decomposition and transformation from one form to another while the excipient content remained constant [22]. Previous work has demonstrated the use of beam enhancer technology with TRS to improve signal to noise and/or speed of data acquisition of TRS measurements [22].…”

“…The most recent work demonstrated the capability of quantifying low (0.62 -1.32% w/w) levels of polymorph content, and additionally the sole decomposition and transformation from one form to another while the excipient content remained constant [22]. Previous work has demonstrated the use of beam enhancer technology with TRS to improve signal to noise and/or speed of data acquisition of TRS measurements [22]. The Beam Enhancer is a dielectric bandpass filter that reflects laser radiation back towards the sample, the majority of which scatters away from the sample and would otherwise reduce the number of photons able to scatter through the sample matrix.…”