Formulation and Evaluation of Solid Dispersion of Celecoxib

Abstract

The aim of this study was to develop celecoxib (CLX) -polyvinylpyrrolidone (PVP) solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS) process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on nanoparticle formation and dissolution as well as oral absorption of CLX -PVP K30 solid dispersion nanoparticles was investigated. Spherical CLX solid dispersion nanoparticles <300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that CLX existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The CLX -PVPTPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of CLX relative to that of the unprocessed form. The area under the concentration-time curve (AUC0 24 h) and peak plasma concentration (Cmax) increased 4.6 and 5.7 times, respectively, with the CLX -PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of CLX -PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble CLX.