Formulation, characterization, and in vivo evaluation of celecoxib-PVP solid dispersion nanoparticles using supercritical antisolvent process.

Eun-Sol Ha,Min-Soo Kim,In-Hwan Baek,Gwang-Ho Choo

doi:10.3390/molecules191220325

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 solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.

Highlights

Celecoxib, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide, is a poorly water-soluble drug belonging to the class of selective cyclooxygenase-2 (COX-2) inhibitors and is clinically used in the treatment of acute pain, rheumatoid arthritis, and osteoarthritis [1]
Our group recently reported that of the 71 combination formulations we evaluated, the most efficient ternary solid dispersion for enhanced bioavailability of sirolimus was the hydroxypropyl methylcellulose (HPMC)/d- α-tocopheryl polyethylene glycol 1000 succinate (TPGS) followed by the HPMC/Sucroester 15 [13]
All celecoxib-PVP K30 solid dispersion nanoparticles had regular spherical shape with particle size range of 150–158 nm and specific surface area of 78–81 m2/g, indicating there was no significant difference between the celecoxib-PVP K30 solid dispersion nanoparticle formulations

Summary

Introduction

4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide, is a poorly water-soluble drug belonging to the class of selective cyclooxygenase-2 (COX-2) inhibitors and is clinically used in the treatment of acute pain, rheumatoid arthritis, and osteoarthritis [1]. Solid dispersion is well established as a formulation system for enhancing the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). Most poorly water-soluble APIs exist in an amorphous form within the solid dispersion, thereby enhancing their dissolution and oral absorption by attaining a highly supersaturated state above their equilibrium solubility. It has been reported that solid dispersion nanoparticles can be manufactured using supercritical fluid technology. Solid dispersion nanoparticles manufactured with hydrophilic polymers and surfactants using the SAS process significantly improved the solubility, dissolution, and oral bioavailability of poorly water-soluble APIs such as atorvastatin calcium, azithromycin, dutasteride, lercanidipine, nilotinib, valsartan, tadalafil and telmisartan [15,16,17,18,19,20,21,22,23]

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