FTIR studies on differential intermolecular association in crystalline and amorphous states of structurally related non-steroidal anti-inflammatory drugs.
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.
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab, 160 062, India.
Aditya M
AM
Kaushal
Asit K
AK
Chakraborti
Arvind K
AK
Bansal
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D000077613:Etoricoxib; D006860:Hydrogen Bonding; D007555:Isoxazoles / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013449:Sulfonamides / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry; D000096926:Benzenesulfonamides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000068579:Celecoxib; D000077613:Etoricoxib; D007555:Isoxazoles; D007783:Lactones; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; C406224:valdecoxib; D000096926:Benzenesulfonamides