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Indomethacin polymorphs: Experimental and conformational analysis

✍ Scribed by J.M. Aceves-Hernandez; I. Nicolás-Vázquez; F.J. Aceves; J. Hinojosa-Torres; M. Paz; V.M. Castaño

Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
346 KB
Volume
98
Category
Article
ISSN
0022-3549

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✦ Synopsis

Thermal analysis of indomethacin alpha and gamma polymorphs presents a temperature transition at 429.2 and 435.8 K, respectively, although with X-ray diffraction or near infra-red spectroscopy phase transformations were not registered. DSC method for the indomethacin amorphous solid shows an endothermic event; however, the conformational analysis at higher temperature shows a rotational change which may explain such endothermic peak. By heating the gamma polymorph at 483 K (210 degrees C) for 30 min and then quenching into liquid nitrogen the amorphous solid was obtained. The alpha form shows the highest intrinsic dissolution rate, while the lowest rate was for the amorphous indomethacin. Theoretical calculations (ab initio, Hartree-Fock and density functional theory, DFT) indicate that the double interaction is responsible for the observed difference in solubility.

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