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Methods for Increasing Sensitivity and Throughput of Solid-State NMR Spectroscopy of Pharmaceutical Solids

Schieber, Loren J.
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Abstract
Solid-state nuclear magnetic resonance (SSNMR) spectroscopy has been demonstrated to be a powerful technique for investigating solid dosage formulations. SSNMR has the ability to determine physical form, molecular structure, and dynamics of a pure or formulated active pharmaceutical ingredient (API). To overcome the major shortcomings of SSNMR, acquisition time and sensitivity, a two-sample probe was designed, developed, and tested. The probe allowed for two samples to be acquired simultaneously while being shuttled through the magnet bore with a stepper motor, and exhibited signal to noise ratio (SNR) values comparable to current probes. Pharmaceutical relevance was demonstrated by acquiring spectra of ibuprofen and aspirin simultaneously. 19F SSNMR was used to examine low-level amorphous impurities in crystalline physical mixtures. The model compound was chosen for amorphous form stability, cost, and 19F SSNMR spectral resolution between the crystalline and amorphous solid forms. Triamcinolone was selected for quantitation studies using 19F SSNMR.
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Date
2010-01-22
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Publisher
University of Kansas
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Keywords
Pharmaceutical chemistry, Amorphous, Fluorine, Nmr, Oxygen, Relaxation, Solid-state
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