Determination of active ingredi- ents in solid (pharmaceutical) dosage forms utilizing solid- state standard additions

Significance of Topic

Near-infrared spectroscopy (NIRS) offers rapid, non-destructive analysis of pharmaceutical solids, enabling content uniformity testing without sample dissolution or complex preparation. Using second-derivative spectra with solid-state standard additions, this approach addresses matrix effects and sample packing variability, streamlining quality control in pharmaceutical manufacturing.

Objectives and Study Overview

This study compares two leading analgesics - aspirin and acetaminophen - and their generic counterparts to assess content uniformity using NIRS. By applying a solid-state standard addition method and second-derivative spectral analysis, the aim is to quantify active ingredients accurately across different dosage forms.

Methodology and Instrumentation

• Instrumentation
  FOSS NIRSystems Model 6500 NIR spectrophotometer with remote reflectance fiber-optic probe; recommended modern alternative: NIRS XDS RapidContent Analyzer.
• Sample Preparation
  Tablets from proprietary (Bayer, Tylenol) and generic sources were ground and spiked with known active ingredient levels (25–200% of label claim).
• Holders Used
  Closed cup, single tablet holder, and 1x10 mm Teflon mini-cup to optimize sample presentation.
• Calibration and Analysis
  Multiple linear regression on second-derivative spectra counters particle-size and packing variation; standard addition calibrations predict individual tablet content.

Main Results and Discussion

• Content Uniformity
  Both aspirin (325 mg) and acetaminophen (500 mg) tablets met pharmacopeial criteria (90–110% of label claim), with proprietary and generic samples showing average recoveries close to 100%.
• Precision Comparison
  Results rival HPLC precision; NIRS reproducibility is within 2% relative to USP limits for HPLC duplicate injections.
• Sampling Variability
  Mini-cup and adjusted single-tablet holders provided consistent spectra with minimal intra-sample variation, demonstrating robustness across different dosage forms.

Benefits and Practical Applications

• Rapid, solvent-free analysis reduces waste and sample preparation time.
• Non-destructive testing preserves tablets for further analysis or release.
• Ease of use and adaptability to multi-component formulations facilitate in-process and final quality control.

Future Trends and Potential Applications

• Integration with PAT (Process Analytical Technology) platforms for real-time monitoring of tablet production.
• Advances in chemometric algorithms and portable NIR devices to support on-site quality assurance.
• Extension to more complex formulations and on-line content uniformity assessment during manufacturing.

Conclusion

Solid-state standard addition combined with second-derivative NIR spectroscopy provides a reliable, precise, and efficient method for tablet content uniformity testing, offering a viable alternative to traditional chromatographic techniques in pharmaceutical QC.