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

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.