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Indomethacin

Indomethacin is a non-steroidal anti inflammatory pharmaceutical drug used for pain relief from conditions like Arthritis. Like many Pharmaceutical drugs, Indomathicic can pack into many different solid forms:

  • Polymorphs: Awaiting description
  • Co-crystals: Awaiting description

The physicochemical properties of a substance is often determined by inter molecular bonding strength which in turn is determined by the efficiency of the packing of molecules, therefore different solid forms of the same molecule may behave differently in the body.

To understand the physicochemical properties it is necessary to determine the structure of the solid form and this is where NMR comes into its own as a technique of utmost importance.

The structure of a solid displaying long range order may be determined by x-ray diffraction, however this method fails as order breaks down (i.e. in amorphous solids). In this case solid state NMR may be used to infer structural properties.


An example of the limitations of x-ray diffraction can be seen in the paper by Aceves-Hernandez et al. Three solid forms of the Indomethacin molecule (two crystalline and one amorphous form) are subjected to x-ray diffraction with the following results...

xray_crystallography.jpg 
J. Pharm. Sci. Vol.98, no. 7 Pages 2448-2463, Fig 3.
Copyright © 2009 Wiley-Liss, Inc., A Wiley Company. Reprinted with permission of John
Wiley & Sons, Inc.

 

The overlap between the different patterns is unfortunate, but it is still possible to see that solid form A has no diffraction peaks, whereas B and C do (although different from eachother). A clearly does not display long range order and is infact an amorpheous form of Indomethacin, whereas B and C are both crystalline polymorphs.


Indomethacin forms of Interest

Below is a table of the Indomethacin solid forms used throughout this project.

Gamma

Alpha

Saccharin co-crystal

One Indomethacin Molecule per assymetric cell. Three Indomethacin molecules per assymetric unit cell. Two bonded through a carboxilic dimer and the third hydrogen bonded to one of the other molecules. An Indomethacin-Saccharin co-crystal can be formed by mechanically grinding the sweetener Saccharin with Indomethacin Gamma. (Vitaram et al)
Gamma alpha saccharin

 

 

indo.jpg

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