Formulation, Characterization, and in Vivo Evaluation of Celecoxib-PVP Solid Dispersion Nanoparticles Using Supercritical Antisolvent Process

Abstract

Abstract:The aim of this study was to develop celecoxib-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 celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib 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 celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS OPEN ACCESSMolecules 2014, 19 20326 solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.

Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process

“…In particular, megestrol acetate-HPMC-TPGS particles exhibited some aggregation and had a specific surface area of 33.1 m 2 /g owing to the low melting temperature of TPGS (approximately 37°C), as previously reported. 15 , 18 , 23 Nonetheless, the mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. The major characteristic crystalline peaks and an endothermic peak at approximately 218°C of megestrol acetate were not observed for any solid dispersion nanoparticles, as evaluated by PXRD and DSC measurements and depicted in Figures 3 and 4 , respectively.…”

Pure Trans-Resveratrol Nanoparticles Prepared by a Supercritical Antisolvent Process Using Alcohol and Dichloromethane Mixtures: Effect of Particle Size on Dissolution and Bioavailability in Rats

“…Pure trans-resveratrol nanoparticles were prepared by the SAS process, as previously reported [35][36][37]. To prepare the sample solution, raw trans-resveratrol (30 mg/g) was dissolved in alcohol (methanol or ethanol) and dichloromethane at different weight ratios (alcohol: dichloromethane; 25:75, 50:50, 75:25, 100:0 w/w) in an amber vial.…”

Celecoxib inhibits mitochondrial O2 consumption, promoting ROS dependent death of murine and human metastatic cancer cells via the apoptotic signalling pathway

“…Interestingly, patients given 200mg celecoxib + 200-mg ketoconazole daily for 7 days to inhibit CYP enzymes showed the highest Cmax 12 µM, with no side effects[55]. More recent advances in drug delivery based around mixtures of polyvinylpyrolidone (PVP)/ d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) as solid dispersion nanoparticles[57] or supersaturating self-emulsifying drug delivery systems (S-SEDDS)[58] have significantly increased the dissolution and orally administered bioavailability of celecoxib. The area under the concentration-time curve (AUC 0→24 h) and peak plasma concentration (Cmax) was increased several fold using celecoxib-PVP-TPGS formulations[57] or S-SEDDS with the highest Cmax reaching 8 µg/ml (or 20 µM) in rat plasma after 3-4 hours[58,59].…”