title: Differential molecular interactions between the crystalline and the amorphous phases of celecoxib.
abstract: We have investigated the differences in molecular interactions between the crystalline (ordered) and amorphous (disordered) phase of a poorly soluble drug, celecoxib. Molecular interactions in the crystalline phase were investigated with the help of Mercury software, using single crystal X-ray diffractometric data for celecoxib. A simulated annealing molecular dynamics approach was used for the assessment of altered molecular interactions in the amorphous phase. Crystalline celecoxib was found to contain an ordered network of H-bonding between all its electron donors (-S=O group, 2-N of pyrazole ring and -C-F) and the acceptor (-N-H). Amorphous celecoxib retained all these interactions in its disordered molecular arrangement, with a relatively stronger H-bonding between the interacting groups, as compared with crystalline celecoxib. However, these inter-molecular interactions differed in strength in the two solid-state forms. The altered configurations of the molecular arrangement in the two phases were supported by the shifts observed in the Fourier-transform infra-red vibrational spectra of respective states. These interactions could have strong implications on devitrification kinetics of amorphous celecoxib, and could further guide the choice of stabilizers for the amorphous form.
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160 062, India.
authors.forename: Piyush
authors.initials: P
authors.lastname: Gupta
authors.forename: R
authors.initials: R
authors.lastname: Thilagavathi
authors.forename: Asit K
authors.initials: AK
authors.lastname: Chakraborti
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Bansal
mesh_terms: D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D011720:Pyrazoles / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib