title: Effect of different "states" of sorbed water on amorphous celecoxib.
abstract: Glass transition temperature (Tg) of an amorphous drug is a vital physical phenomenon that influences its visco-elastic properties, physical, and chemical stability. Water acts as a plasticizer for amorphous drugs thus increasing their recrystallization kinetics. This reduces the solubility advantage of an amorphous drug. Hence, there is an interest in understanding the relationship between water content and Tg of amorphous drug. We have studied the effect of "state" of sorbed water on Tg of amorphous celecoxib (ACLB). ACLB was allowed to sorb water at relative humidity of 33%, 53%, 75%, and 93%. ALCB showed biphasic sorption of water designated as "bound" and "solvent-like" state of water associated with ACLB. Molecular modeling studies provided deeper insights into the interaction of water with ACLB. A distinct co-relationship between the state of water and its plasticization capacity was observed. Bound state of water had a very profound effect on the fall in experimentally observed Tg (T(g-exp)) value. Solvent-like state of water had little impact on T(g-exp) value. Tg of ACLB-water mixture was predicted by Gordon-Taylor equation (T(g-pre)). The deviations in T(g-exp) and Tg-pre were correlated to volume non-additivity and non-ideal mixing. This study has implications on the development of formulations based on amorphous forms.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062 India.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Shete
authors.affiliation: Generics FR&D, Dr. Reddy's Laboratories, Bachupally, Hyderabad 500072, India.
authors.forename: Swathi
authors.initials: S
authors.lastname: Kuncham
authors.affiliation: Novartis-MIT Centre for continuous manufacturing, Cambridge, Massachusetts 02139.
authors.forename: Vibha
authors.initials: V
authors.lastname: Puri
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062 India.
authors.forename: Rahul P
authors.initials: RP
authors.lastname: Gangwal
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062 India.
authors.forename: Abhay T
authors.initials: AT
authors.lastname: Sangamwar
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062 India. Electronic address: akbansal@niper.ac.in.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Bansal
mesh_terms: D065966:Absorption, Physicochemical; D002152:Calorimetry, Differential Scanning; D000068579:Celecoxib; D003460:Crystallization; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry*; D008859:Microscopy, Polarization; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry*; D014783:Viscosity; D014835:Volatilization; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014867:Water; D000068579:Celecoxib
keywords: Amorphous; glass transition; molecular modeling; water in solids; water sorption