Quantifying Pharmaceutical Formulations from Proton Detected Solid-State NMR under Ultrafast Magic Angle Spinning
| Autor: | Xingyu Lu, Haichen Nie, Michael J. McNevin, Wei Xu, Yongchao Su, Gregory M. Troup, Mingyue Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Active ingredient
Detection limit Materials science Magnetic Resonance Spectroscopy Resolution (mass spectrometry) Drug Compounding Analytical chemistry Pharmaceutical Science Free base 02 engineering and technology 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy Magnetic Resonance Imaging Excipients 03 medical and health sciences 0302 clinical medicine Solid-state nuclear magnetic resonance Magic angle spinning Molecule Binary system Protons 0210 nano-technology |
| Zdroj: | Journal of pharmaceutical sciences. 109(10) |
| ISSN: | 1520-6017 |
| Popis: | Probing form conversions of active pharmaceutical ingredients in solid dosages is critical for understanding the physicochemical stability of drug substances in formulations. The multicomponent and low drug loading nature of drug products often results in challenges to quantify the phase stability, at a low detection limit and with the chemical resolution that differentiate drug molecules and excipients, for routine laboratory techniques. Recent advancement of ultrafast magic angle spinning (UF-MAS) enables proton-detected solid-state nuclear magnetic resonance (ssNMR) techniques to characterize pharmaceutical materials with enhanced resolution and sensitivity. This study demonstrates one of the first documented cases implementing 60 kHz UF-MAS techniques to quantify the minor content of pioglitazone free base (PIO-FB) in a binary system with its hydrochloride salt (PIO–HCl) and a multicomponent formulation with typical excipients. One-dimensional 1H methods can unambiguously differentiate the two forms and exhibit a limit of detection at 1.77% (w/w). Moreover, we extended it to a two-dimensional 1H–1H correlation for minimizing peak overlap and successfully quantifying approximately 2.0% (w/w) PIO-FB in a multicomponent formulation. These results have demonstrated that 1H ssNMR as a novel method to quantify solid dosages at a higher resolution and faster acquisition than conventional 13C techniques. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|