Encapsulation of Indomethacin in PVP: Solid‐State NMR Studies

Abstract

13 C solid-state NMR and 1 H relaxation time measurements have been used to determine the structure of the crystalline and amorphous forms of the pharmaceutical drug indomethacin. Cross-polarization dynamics parameters were calculated for individual NMR resonances providing an insight into the mobility of functional groups in two forms of indomethacin. The changes of mobility in indomethacin/ polyvinylpyrrolidone (PVP) formulation have been investigated via 1 H-13 C solid-state NMR methods. Differences between the amorphous material and its crystalline counterpart have been observed. The g-amorphous indomethacin rapidly crystallizes with time. It has been shown that encapsulation in the PVP stabilizes the amorphous form of the drug by preventing crystallization due to reduced mobility of the guest in the formulation.

Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph

“…[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Recent studies by Surwase et al reported new crystalline forms of IMC and water driven phase transitions from an amorphous phase, in spite of years of studies. 23 The thermodynamically most stable form of indomethacin (g-IMC) has the space group symmetry P% 1 with Z 0 = 1.…”

Understanding Surface and Interfacial Chemistry in Functional Nanomaterials via Solid‐State NMR

“…Possible changes include the interconversion of different crystalline forms, hydrate formation, or chemical degradation. In particular, polymorphic changes of the API, may lead to significant effects on their bioactivity . The stability of the drug formulations is also another fundamental requirement for pharmaceutical development and commercialization .…”

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.…”