title: Molecular interactions in celecoxib-PVP-meglumine amorphous system.
abstract: Stabilization of the amorphous form of a drug is conferred by additives that interact with it at the molecular level. Ternary systems of celecoxib, poly(vinyl pyrrolidone) (PVP) and meglumine were studied for molecular interactions responsible for enhanced drug stability and solubility in amorphous form. Meglumine was found to lower the glass transition temperature (T(g)) of the drug due to its plasticization effect. However, the presence of PVP masked its destabilizing effect and provided net anti-plasticization to the celecoxib-PVP-meglumine (7:2:1 w/w) ternary amorphous system. Positive deviation of the experimentally determined T(g mix) value for this composition, from those predicted by the Gordon-Taylor/Kelley-Bueche equation, inferred molecular interaction between the three species, which was also supported by band shifts from their Fourier-transform infra-red (FTIR) spectra. Further, shift of differential scanning calorimetry (DSC) melting endotherms of celecoxib in its amorphous systems from those observed for crystalline celecoxib confirmed the complexation between these components, which was also substantiated by molecular modelling studies that showed H-bonding of -S=O, 2-N of the pyrazole ring and -C-F groups of celecoxib with -O-H group of meglumine. These molecular interactions of amorphous celecoxib with meglumine were found to be the potential cause for enhanced stability and solubility of the celecoxib-PVP-meglumine ternary system.
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab 160 062, India.
authors.forename: Piyush
authors.initials: P
authors.lastname: Gupta
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Bansal
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D000068579:Celecoxib; D004355:Drug Stability; D008536:Meglumine / Q000737:chemistry*; D008958:Models, Molecular; D011205:Povidone / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D008536:Meglumine; D011205:Povidone; D000068579:Celecoxib