Indomethacin polymorphs: Experimental and conformational analysis

Thermal analysis of indomethacin α and γ 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 γ polymorph at 483 K (210°C) for 30 min and then quenching into liquid nitrogen the amorphous solid was obtained. The α 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. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2448-2463, 2009