Structure determination, thermal stability and dissolution rate of 6-indomethacin

被引：27

作者：

Andrusenko, Iryna ^{[1
]}

Hamilton, Victoria ^{[2
]}

Lanza, Arianna E. ^{[1
]}

Hall, Charlie L. ^{[2
]}

Mugnaioli, Enrico ^{[1
]}

Potticary, Jason ^{[2
]}

Buanz, Asma ^{[3
]}

Gaisford, Simon ^{[3
]}

Piras, Anna M. ^{[4
]}

Zambito, Ylenia ^{[4
]}

Hall, Simon R. ^{[2
]}

Gemmi, Mauro ^{[1
]}

机构：

[1] Ist Italiano Tecnol, Ctr Nanotechnol Innovat NEST, Piazza San Silvestro 12, I-56127 Pisa, Italy

[2] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England

[3] UCL, UCL Sch Pharm, 29-39 Brunswick Sq, London WC1N 1AX, England

[4] Univ Pisa, Dept Pharm, Via Bonanno 33, I-56126 Pisa, Italy

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2021年 / 608卷

基金：

英国工程与自然科学研究理事会; 欧盟地平线“2020”;

关键词：

Electron diffraction; Structure determination; Pharmaceutical compounds; Polymorphism; Bioavailability; Indomethacin; Non-steroidal anti-inflammatory drugs; 3D ELECTRON-DIFFRACTION; INDOMETHACIN POLYMORPHS; CRYSTAL-STRUCTURE; DRUG; COCRYSTAL; STATE; NANOCRYSTALS; SPECTROSCOPY; SOLUBILITY; SYSTEM;

D O I：

10.1016/j.ijpharm.2021.121067

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The structure solution of the 6-polymorph of indomethacin was obtained using three-dimensional electron diffraction. This form shows a significantly enhanced dissolution rate compared with the more common and better studied alpha- and gamma-polymorphs, indicating better biopharmaceutical properties for medicinal applications. The structure was solved in non-centrosymmetric space group P21 and comprises two molecules in the asymmetric unit. Packing and molecule conformation closely resemble indomethacin methyl ester and indomethacin methanol solvate. Knowledge of the structure allowed the rational interpretation of spectroscopic IR and Raman data for 6-polymorph and a tentative interpretation for still unsolved indomethacin polymorphs. Finally, we observed a solid-solid transition from 6-polymorph to alpha-polymorph that can be driven by similarities in molecular conformation.

引用

页数：10

共 59 条

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