Flip-back, an old trick to face highly contrasted relaxation times: Application in the characterization of pharmaceutical mixtures by CPMAS NMR

Abstract

The 13C– 1H CPMAS with flip-back pulse NMR experiment is revisited in view of applications to pharmaceutical mixtures. The analysis of the kinetics of relaxation and CP transfer with and without the flip-back pulse shows that a significant gain in 13C signal can be expected (thus in experimental time) from the flip-back pulse for protons with long T 1. The gain is of the order of T 1 of the protons expressed in seconds. The experiment is applied on samples with highly contrasted spin-lattice relaxation times T 1 for protons, situation encountered in pharmaceutical mixtures. The application of the flip-back increases significantly the relative signal intensity of the component with the longer T 1, making this component detectable even after using short recycle delays. Therefore, this CPMAS with flip-back experiment could be used routinely to get 13C CPMAS NMR spectra of mixtures in constant experimental time and signal-to-noise ratio without the need for optimization of the recycle delays, and for whatever may be the degree of crystallinity of the active principal ingredient (API) and/or excipients.