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Rapid Characterization of Formulated Pharmaceuticals Using Fast MAS 1H Solid-State NMR Spectroscopy
David A Hirsh1, Anuradha V Wijesekara1, Scott L Carnahan1
1Department of Chemistry , Iowa State University , Ames , Iowa 50011 , United States.
Molecular Pharmaceutics
|May 17, 2019
Summary
New 1H solid-state NMR (SSNMR) methods rapidly characterize low drug-loaded formulations. This technique enhances sensitivity and reduces experiment time for analyzing active pharmaceutical ingredients (APIs) in tablets.
Area of Science:
- Pharmaceutical Sciences
- Analytical Chemistry
- Solid-State NMR Spectroscopy
Background:
- Active pharmaceutical ingredients (APIs) exist in various solid forms impacting oral dosage form performance.
- Characterizing API phases in drug products is crucial for development and commercialization.
- Standard 13C solid-state NMR (SSNMR) faces sensitivity and excipient interference challenges with low API loading.
Purpose of the Study:
- To develop a rapid and sensitive analytical technique for characterizing low drug-load formulations.
- To overcome the limitations of 13C SSNMR for analyzing APIs in complex dosage forms.
- To enable efficient phase determination of APIs within tablets.
Main Methods:
- Utilized fast magic angle spinning 1H SSNMR experiments.
- Employed frequency-selective saturation and excitation pulses to suppress excipient signals.
- Incorporated two-dimensional experiments and 1H spin diffusion for enhanced spectral clarity.
- Demonstrated selective saturation for efficient suppression of common excipient signals (lactose, cellulose).
Main Results:
- Achieved rapid characterization of low drug-load formulations using 1H SSNMR.
- Obtained diagnostic 1H SSNMR spectra of APIs within tablets by suppressing excipient interference.
- Demonstrated a 100- to 1000-fold reduction in experiment time compared to 13C SSNMR.
- Showcased the potential for quantitative analysis of APIs in tablets via 1H SSNMR.
Conclusions:
- Fast 1H SSNMR is a highly effective technique for rapid characterization of low API load formulations.
- This method significantly reduces experiment times, enabling efficient analysis of APIs in tablets.
- 1H SSNMR offers a sensitive and practical alternative to 13C SSNMR for analyzing drug products.
Keywords:
active pharmaceutical ingredientsmolecular structureoral dosage formsphase characterizationpolymorphMore Related Videos
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