Study and characterization of crystalline hydrate/polymorph forms of 5,11-dihydro-11-ethyl-5-methyl-8-(2-(1-oxido-4-quinolinyl)ethyl-6H-dipyrido(3,2-B:2′,3′-E)(1,4)diazepin-6-one by solid-state NMR and solution NMR

A novel inhibitor of reverse transcriptase was studied by solid-state NMR. Three phases of the compound were examined which included the dihydrate and two anhydrous polymorphs (Form I and Form III). By correlating 1H and 13C solution NMR with the solid-state 13C NMR CP/MAS and CPPI spectral editing experiments, comparative 13C assignments were made for each phase. Polymorphs of Form I and Form III and the dihydrate were easily distinguished based upon chemical shift patterns of the carbon resonances. The 1H spin-lattice relaxation times were also measured for each phase which provided information on the mobility and relative crystallinity. The 13C ssNMR spectrum of Form I showed the presence of a minor component identified as the dihydrate. Weight/percent quantitation of major and minor components in Form I was obtained from integrated intensities of a 50:50 mixture containing weighed amounts of Form I and the pure dihydrate. Comparison of the ssNMR and X-ray powder diffraction techniques is discussed.