Structural basis for the transformation pathways of the sodium naproxen anhydrate–hydrate system

IUCrJ

Qu, H.¹  Larsen, F.H.²  Cornett, C.³  Raijada, D.³  Rantanen, J.³  Bond, A.D.³ 

[1] Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Niels Bohrs Alle 1, Odense DK-5230, Denmark;Department of Food Science, University of Copenhagen, Rolighedsvej 30, Frederiksberg DK-1958, Denmark;Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark

关键词: PHARMACEUTICAL;    HYDRATE;    X-RAY DIFFRACTION;    SOLID-STATE NMR;    DFT-D;   

DOI  :  10.1107/S2052252514015450

学科分类：数学（综合）

来源: International Union of Crystallography

【 摘 要 】

Crystal structures are presented for two dihydrate polymorphs (DH-I and DH-II) of the non-steroidal anti-inflammatory drug sodium (S)-naproxen. The structure of DH-I is determined from twinned single crystals obtained by solution crystallization. DH-II is obtained by solid-state routes, and its structure is derived using powder X-ray diffraction, solid-state 13C and 23Na MAS NMR, and molecular modelling. The validity of both structures is supported by dispersion-corrected density functional theory (DFT-D) calculations. The structures of DH-I and DH-II, and in particular their relationships to the monohydrate (MH) and anhydrate (AH) structures, provide a basis to rationalize the observed transformation pathways in the sodium (S)-naproxen anhydrate–hydrate system. All structures contain Na+/carboxylate/H2O sections, alternating with sections containing the naproxen molecules. The structure of DH-I is essentially identical to MH in the naproxen region, containing face-to-face arrangements of the naphthalene rings, whereas the structure of DH-II is comparable to AH in the naproxen region, containing edge-to-face arrangements of the naphthalene rings. This structural similarity permits topotactic transformation between AH and DH-II, and between MH and DH-I, but requires re-organization of the naproxen molecules for transformation between any other pair of structures. The topotactic pathways dominate at room temperature or below, while the non-topotactic pathways become active at higher temperatures. Thermochemical data for the dehydration processes are rationalized in the light of this new structural information.

【 授权许可】

CC BY