FTIR studies on differential intermolecular association in crystalline and amorphous states of structurally related non-steroidal anti-inflammatory drugs

Abstract

Information on molecular interactions critically impacts the physical stability and "stabilization" strategy for the amorphous state of pharmaceuticals. The present study was designed to understand the differences in intermolecular interactions in amorphous and crystalline phases in a series of structurally related compounds-celecoxib (CLB), valdecoxib (VLB), rofecoxib (RFB), and etoricoxib (ETB). FTIR spectra of the compounds in their crystalline and amorphous phase were obtained. Interaction patterns in respective crystalline states were obtained from single crystal data. The intermolecular interaction patterns varied between the crystalline and amorphous phase of CLB, VLB, and ETB, while no variation was observed for RFB. Comparison of four crystalline phases though revealed significantly variations, the interactions were remarkably similar in the amorphous state, possibly as a result of constraints of crystal packing ceasing to exist. Conversion of crystalline state to amorphous state led to weakening of some interactions while others got strengthened. The differences in intermolecular interactions could successfully explain the differences in thermodynamic properties studied previously (Kaushal, A. M.; Bansal, A. K. Thermodynamic behavior of glassy state of structurally related compounds. Eur. J. Pharm. Biopharm. 2008, 69, 1067−1076.).