Entrapment of celecoxib into mesoporous silica particles for tablets with improved dissolution through amorphization

The objective of this study was to develop mesoporous silica particles (MSPs) tablet that can entrap large amounts of celecoxib into the mesopores as an amorphous state, exhibiting an enhanced dissolution. Optimal conditions that enable high drug loading into MSPs were investigated. The crystallinity was evaluated by X-ray scattering and morphology observation. The anti-inflammatory activity of celecoxib and celecoxib-loaded MSPs was compared in the lipopolysaccharide-stimulated Raw264.7 cells via quantification of nitric oxide. The optimal MSP formulation was manufactured into the tablet. Dissolution of the tablet was evaluated in pH 1.2 and 6.8 buffer and compared with that of commercial celecoxib (Celebrex®). The highest entrapment capacity (12.4%) was achieved when using incipient wetness impregnation method to MCM-41 at the equal ratio to the drug. In all MSP formulations, considerable decreases in the drug crystallinity were observed. The optimal formulation showed about 3-fold increase in the drug apparent solubility against raw materials. The production of nitric oxide in the lipopolysaccharide-stimulated Raw264.7 cells was significantly decreased by celecoxib-loaded MSPs at 25 μM (corresponding to entrapped celecoxib), which was similar to the activity of celecoxib. The MSP tablet formulation exhibited rapid disintegration shorter than 30 s and improved dissolution in both pH conditions than those of Celebrex®. This work suggests a successful strategy for the formulation of MSP tablets that allow high loading of celecoxib in MSPs as the amorphous state leading to an improved dissolution.