Preparation and in vivo evaluation of immediate-release pellet containing celecoxib solid dispersion

Abstract

The aim of this study was to make use of small size of immediate-release (IR) pellet and amorphous state of solid dispersion to increase solubility of celecoxib (CLX), a drug in BCS class II. Primary, binary and ternary solid dispersions were developed to choose the final components for solid dispersion. A ternary novel solid dispersion was prepared by incorporation of one aqueous soluble polymer (povidone k17; PVP 17PF), Methacrylate copolymer-based gastric soluble polymer (Eudragit® EPO) and one pH modulator (MgO). This combination was effective to increase solubility in pH 1.2 up to 25–30 %. The mechanism of solubility enhancement was proven by DSC, PRXD, and FT-IR. Accordingly, hydrogen bonding or electrostatic interaction of CLX with PVP/Eudragit® EPO was the main cause to form the amorphous state of CLX within polymer cluster which increasing solubility of drug. Besides, MgO played an important role to change microenviroment for solid dispersion. Pellets containing this solid dispersion were prepared by extrusion and spheronization technique. Effect of four kinds of additive (calcium hydrogen phosphate dihydrate, NaHCO3, crospovidone, and sodium dodecyl sulfate) on dissolution of CLX from IR pellet was also determined. Because of highest dissolution rate, formulation using sodium dodecyl sulfate was used for pharmacokinetics study. Solid dispersion-IR pellet formulation presented bioequivalence and lower variability in comparison with reference product.