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

• Published in: Journal of pharmaceutical and biomedical analysis 2010-04, Vol.51 (5), p.1047-1053
• Main Authors: Gonnella, N.C., Smoliga, John A., Campbell, Scot, Busacca, Carl A., Cerreta, Michael, Varsolona, Richard, Norwood, Daniel L.
• Format: Article
• Language: English
• Subjects: 13C solid-state NMR; 1H relaxation; Azepines - chemistry; Chemical shift assignments; Crystallization; Crystallography, X-Ray; Degree of crystallinity; Magnetic Resonance Spectroscopy; Molecular Structure; Powder Diffraction; Pyridines - chemistry; Rapid quantitation; Reverse Transcriptase Inhibitors - chemistry; Technology, Pharmaceutical - methods; Water - chemistry
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2009.11.012

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.