Amorphous multi-system of celecoxib improves its anti-inflammatory activity in vitro and oral absorption in rats

Abstract

In the present study, a multi-system for solid dispersion (SD) of celecoxib (CXB) was designed to improve its solubility and anti-inflammatory effects in vitro as well as oral absorption in rats. The SD formulations were prepared by a solvent evaporation with a multi-system as the solubilizer; an alkalizer; and fumed silica (Aerosil® 200). The physicochemical properties of the SD formulations were evaluated. Polyoxyl 15 hydroxystearate (HS 15®) was chosen as the solubilizer based on the apparent solubility test. The optimal SD formulation (SD6, CXB: HS 15®: K30®: meglumine: Aerosil® 200 = 200: 50: 50: 100: 100, weight ratio) improved the dissolution (%) over 2-fold compared to that by the commercial product (Celebrex®) at pH 1.2, in distilled water (DW), and in a pH 6.8 buffer (sodium lauryl sulfate [SLS], 0.25% w/v). The SD6 formulation altered physical properties such as crystallinity, thermal stability, and intra-molecular interaction. Moreover, SD6 showed a good stability for 6 months. The anti-inflammatory effect of SD6 significantly improved 2.2-fold compared to that of Celebrex® in the cell study. The relative bioavailability (BA) of SD6 was significantly improved to 209.4% compared to that of Celebrex®. In conclusion, intra-molecular interactions between CXB and solubilizers in multi-systems increase its solubility, dissolution (%), anti-inflammatory effects in vitro, and the relative BA (%) in rats. Thus, SD6 would be effective for the treatment of inflammation in rats and should be evaluated in detail in future clinical studies.