betadex and rofecoxib

Rofecoxib (Rb) is a nonsteroidal anti-inflammatory drug (NSAID) with poor aqueous solubility. The present study was undertaken to investigate the influence of water-soluble polymers namely sodium carboxymethyl cellulose (Na CMC), polyvinylpyrrolidine (PVP) and polyethylene glycol (PEG-6000) on hydroxypropyl beta-cyclodextrin (HP beta-CD) complexation of Rb. The complexes were prepared by kneading, autoclaving and precipitation techniques in 1:1 and 1:2 molar ratios. The aqueous solubility enhancement of Rb by these polymers is found to be of the following order: Na CMC > PVP > PEG-6000. Complexes were characterized by Fourier transform infrared (FTIR) spectroscopy, Nuclear magnetic resonance (NMR) and X-ray diffractometry (XRD) techniques. In vitro dissolution studies were carried out on tablets formulated from molar ratios of the complexes prepared by different techniques.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Crystallography, X-Ray; Cyclooxygenase 2 Inhibitors; Drug Compounding; Hypromellose Derivatives; Kinetics; Lactones; Magnetic Resonance Spectroscopy; Methylcellulose; Polymers; Povidone; Solubility; Spectroscopy, Fourier Transform Infrared; Sulfones; Water

Topics: Animals; beta-Cyclodextrins; Chemical Phenomena; Chemistry, Pharmaceutical; Chemistry, Physical; Lactones; Male; Rats; Rats, Wistar; Solubility; Stomach Ulcer; Sulfones; Technology, Pharmaceutical

Complex formation of rofecoxib and beta-cyclodextrin in aqueous solution and in solid state and the possibility of improving the solubility and dissolution rate of rofecoxib via complexation with cyclodextrin were investigated. Phase solubility studies indicated the formation of an 1:1 complex in solution and the value of apparent stability constant was 769 M(-1). Solid inclusion complexes of rofecoxib and cyclodextrin were prepared by the kneading method in different molar ratios. Differential scanning calorimetry studies indicated the formation of solid inclusion complexes of rofecoxib and cyclodextrin at different molar ratios and the solid complexes exhibited a higher rate of dissolution than the physical mixture and the pure drug.

Topics: Algorithms; beta-Cyclodextrins; Buffers; Calorimetry, Differential Scanning; Chemical Phenomena; Chemistry, Physical; Cyclodextrins; Cyclooxygenase Inhibitors; Excipients; Kinetics; Lactones; Solubility; Spectrophotometry, Ultraviolet; Sulfones