A sample wetting strategy to overcome differences in physical morphology between lab-prepared training samples and...

Area of Science:

• Pharmaceutical Analysis
• Spectroscopy
• Materials Science

Background:

• Lab-blended powders are common for multivariate quantitative analysis training sets.
• Pharmaceutical process samples often have granular morphology, differing from lab powders.
• Morphological differences cause dissimilar Raman spectral features, reducing analysis accuracy.

Purpose of the Study:

• To introduce and evaluate a water wetting strategy for harmonizing sample morphologies.
• To improve the accuracy of Raman spectroscopic analysis for pharmaceutical samples.
• To enable accurate quantitative analysis of active pharmaceutical ingredients (APIs) in real process samples.

Main Methods:

• Demonstration of a water wetting technique to alter sample physical presentations.
• Application of the strategy to samples containing esomeprazole magnesium dihydrate (EMD) and other components.
• Development and comparison of partial least squares (PLS) models before and after sample wetting.
• Confirmation of morphological and crystallinity changes using SEM imaging and XRD patterns.

Main Results:

• A PLS model using un-wetted training samples was inaccurate for real process samples.
• Water wetting created similar morphologies in both lab powders and process granules.
• Wetted samples allowed for accurate EMD concentration determination via Raman spectroscopy.
• SEM and XRD confirmed similar morphologies and crystallinities in wetted samples.

Conclusions:

• Water wetting is an effective and simple strategy to improve Raman spectroscopic analysis accuracy.
• The method overcomes challenges posed by morphological differences between training and process samples.
• This versatile technique is applicable to various vibrational spectroscopic analyses of diverse sample types.