Solid-state 13C NMR study of indomethacin polymorphism

Solid-State Carbon NMR Characterization and Investigation of Intrinsic Dissolution Behavior of Fluconazole Polymorphs, Anhydrate Forms I and II

“…21) SSNMR spectroscopy can be used to estimate the number of molecular conformations, as well as the configurational differences, in a portion of the molecule. 22,23) The 13 C-SSNMR spectra of anhydrate form II shows only one peak per carbon atom with no peak splitting. However, the number of form I peaks exceeds the number of carbon with splittings of the a-quaternary carbon and C-1 of 2,4-difluorobenzyl groups.…”

Probing Intermolecular Crystal Packing in γ-Indomethacin by High-Resolution 1H Solid-State NMR Spectroscopy

“…24,25 By employing advances in homonuclear 1 H decoupling that deliver high-resolution 1 H spectra, 26,27 the 1 H-1 H DQ CRAMPS technique [28][29][30][31][32] has been applied to the potassium salt of penicillin characterised anhydrous polymorphs (that are labelled ,  and )  crystal structures are available for the  and  forms. 38,39 13 C CP MAS spectra have been reported for the crystalline polymorphs as well as amorphous forms of indomethacin, 13,[40][41][42] while a recent study has presented 1 H- 13 C and 1 H-1 H DQ twodimensional spectra for an indomethacin-polymer dispersion together with a 1 H-1 H DQ MAS spectrum of -indomethacin. 13 Amorphous forms, dispersions as well as co-crystals of indomethacin have and are being extensively studied on account of the poor solubility exhibited by indomethacin and hence its limited bioavailability.…”

“…The observed spectral resonances are assigned by means of GIPAW chemical shift calculations for the full periodic crystal structure (see Table 1) -indomethacin crystallizes in the centrosymmetric triclinic P1 space group with one molecule in the asymmetric unit. Note that the atom numbering system used here is that employed by Basavoju et al; 44 various alternative numbering schemes have been used in the published single-crystal X-ray structure 39 and other reports of solid-state NMR 13 C CP MAS data by Apperley et al, 40 Masuda et al, 41 Guilbaud et al, 42 and Pham et al 13 currents, that lead to  crystmol changes of at least 1 ppm for the 1 H chemical shift (see Table 1) and (e) 53 and host-guest interactions in molecular tweezers [54][55][56] or calixarene complexes. 57 The distance from the particular proton to the centre of the specific aromatic moiety is 2.72 Å (9b) and 3.12 Å (9a) for the C9 CH 2 protons, 2.68 Å for the nearest C11 CH 3 proton and 3.42 Å for the C16 aromatic CH proton.…”

Polymorphism and Solvatomorphism 2006

“…70 Solidstate 13 C nuclear magnetic resonance spectrometry was used to study differences in molecular conformations in two polymorphs of indomethacin, and was also used to facilitate evaluation of the packing of molecules in the unit cell. 71 The power of solubility analysis to profile polymorphic systems was amply demonstrated in studies of the crystal forms of eflucimibe. 72 Full phase diagrams of the drug substance in pure solvents and solvent mixtures were established, and variable temperature studies conducted between 208C and 558C were used to demonstrate that Form-A was the most stable polymorph in that it exhibited the lowest solubility.…”