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

Abstract

The (13)C-(1)H 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 (13)C 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 (13)C 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.