Overcoming optical focus issues in handheld Raman systems for analysis of pharmaceutical drug formulations

Importance of the Topic

Raman spectroscopy has become a key method for rapid, non-destructive identification and quantification of pharmaceutical formulations. Addressing optical focus challenges in handheld instruments enhances the reliability of field analysis and streamlines quality control workflows.

Study Objectives and Overview

This bulletin evaluates the Orbital Raster Scan (ORS) sampling technique implemented in Metrohm’s Mira M-1 handheld Raman device. The goals were to compare ORS to conventional fixed-spot sampling in terms of signal reproducibility, analysis speed, and spectral matching quality for a multi component effervescent cold medicine.

Methodology and Instrumentation

The study employed the Mira M-1 handheld Raman spectrometer with ORS enabled or disabled. Tablets containing three active pharmaceutical ingredients (aspirin, chlorpheniramine maleate, phenylephrine bitartrate) were measured at 15 random points. Acquisition parameters: 1 s integration, 75 mW laser power.

Used Instrumentation

• Mira M-1 handheld Raman spectrometer with ORS module
• Grams AI software for data processing and Partial Least Squares (PLS) regression

Main Results and Discussion

ORS sampling dramatically increased reproducibility of Raman signals across heterogeneous sample areas. Without ORS, peak intensities varied widely; ORS ON yielded highly congruent spectra. Quantitative PLS models for aspirin concentration improved from R²=0.926 (ORS OFF) to R²=1.0 (ORS ON). Hit Quality Index (HQI) scores for matching to reference spectra rose from 0.94–0.98 (ORS OFF) to a consistent 0.99 (ORS ON). ORS reduced analysis time by 95% compared to multi-point averaging without ORS.

Benefits and Practical Applications

• Enhanced reproducibility and spectral matching for heterogeneous pharmaceutical tablets
• Faster screening and quantification with minimal sample preparation
• Cost-effective alternative to automated stage mapping

Future Trends and Opportunities

Integration of ORS with advanced chemometric techniques (e.g., PCA, machine learning) may further strengthen compliance with regulatory standards. Expanding ORS methods to other solid formulations and complex matrices could broaden field use in QA/QC and counterfeit detection.

Conclusion

The ORS technique in Mira M-1 handheld Raman systems addresses key focus challenges by spatially averaging over a larger area while preserving resolution. This delivers rapid, robust identification and quantification of drug formulations, reducing analysis time and improving data consistency.

Reference

• Metrohm Application Bulletin AB-423/1 e: Overcoming optical focus issues in handheld Raman systems for analysis of pharmaceutical drug formulations