P-test verification of Equate cold tablets and comparison with Alka-Seltzer

Importance of the Topic

Generic over-the-counter drugs often match branded formulas in active ingredients but require verification to guarantee consistent quality, safety, and efficacy.
Raman spectroscopy offers a rapid, nondestructive approach to confirm chemical composition and homogeneity between generic and name-brand tablets.

Objectives and Study Overview

This study aimed to verify Equate effervescent cold relief tablets (generic) against Alka-Seltzer Plus cold formula (branded) by using p-test multivariate analysis with handheld Raman spectroscopy.
Key objectives included establishing a robust spectral training set to capture tablet inhomogeneity and accurately detect subtle differences in ingredient distribution.

Used Methodology and Instrumentation

Methodology:

• Collected spectra from multiple locations on each tablet to build a representative training set (minimum 20 samples).
• Acquisition parameters: 785 nm laser excitation, auto integration, confidence interval 0.95, match score threshold 0.85, average 1 scan.
• Employed p-test multivariate analysis to assess whether sample spectra statistically belong to the training set.

Instrumentation:

• Metrohm Instant Raman Analyzer Mira P Advanced with Orbital Raster Scan (ORS™) technology for enhanced interrogation of heterogeneous samples.
• Short working distance (SWD) attachment for direct tablet analysis through containers.

Main Results and Discussion

The Equate (EQ) training set produced p-values ranging from 0.146 to 0.712 (all > 0.05), confirming internal consistency and robustness.
Comparison of Alka-Seltzer (AS) samples against the EQ training set revealed:

• With ORS ON: most scans yielded p-values below 0.05 (FAIL), indicating significant differences in ingredient distribution.
• With ORS OFF: several scans passed, reflecting localized matching in discrete tablet regions and highlighting inhomogeneity effects.

Although spectral peaks of EQ and AS were qualitatively similar, the variation in active ingredient distribution led to failed verification in most ORS-enabled tests.

Benefits and Practical Applications

• Provides fast, nondestructive verification of active ingredient identity and uniformity in pharmaceutical tablets.
• Ensures generic formulations meet the quality benchmarks of branded products.
• Enhances quality control protocols in manufacturing, distribution, and regulatory compliance.

Future Trends and Opportunities

• Integration of handheld Raman analyzers with cloud-based spectral libraries for real-time verification and remote support.
• Development of advanced chemometric algorithms to detect trace impurities and quantify compositional inhomogeneity.
• Expansion of p-test protocols to additional dosage forms, including capsules, gels, and suspensions.

Conclusion

The Mira P handheld Raman spectrometer, combined with p-test analysis, effectively demonstrated that Equate and Alka-Seltzer cold tablets share similar active components yet differ in ingredient distribution.
ORB™ technology significantly improves confidence in verifying heterogeneous pharmaceutical samples.

References

1. Metrohm AG. Application Note AN-RS-010: P-test verification of Equate cold tablets and comparison with Alka-Seltzer.