Study And Characterization Of Crystalline Hydrate/Polymorph Forms Of 5,11-Dihydro-11-Ethyl-5-Methyl-8-(2-(1-Oxido-4-Quinolinyl)Ethyl-6h-Dipyr Ido(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 H-1 and C-13 solution NMR with the solid-state C-13 NMR CP/MAS and CPPI spectral editing experiments, comparative C-13 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 H-1 spin-lattice relaxation times were also measured for each phase which provided information on the mobility and relative crystallinity. The C-13 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. (C) 2009 Elsevier B.V. All rights reserved.