The Preparation And Characterization Of Celecoxib-poloxamer188-aerosil Solid Dispersion

Celecoxib?CXB?,a nonsteroidal anti-inflammatory drug?NSAID?,is a highly selective COX-II inhibitor.Clinically,it is commonly applied for the cure of acute or chronic osteoarthritis and rheumatoid arthritis symptoms,and can also be used to cure back pain and acute sciatica.Compared with the traditional NSAIDS,CXB is safer and more effective in gastrointestinal,cardiac,renal treatment,and platelet aggregation and therefore gains a promising market prospect.However,CXB is one of the BCS-II drugs with poor water solubility.Dissolution is the limiting factor for its absorption,which leads to its low bioavailability,and individual absorption varies greatly.Solid dispersion,as one of the most prevalent and effective strategies to improve oral bioavailability of poorly water soluble API,has been the focus of recent researches.In SD systems,particle size reduction can not only improve wettability of the poorly water soluble API but also facilitate the dissolution process,therefore,enhance the bioavailability of API.The present study prepared CXB solid dispersion by solvent evaporation,and by selection of proper polymers on the results of dissolution and literature study,Poloxamer188 and Aerosil were chosen as co-polymers.In the selection of dissolution medium,water+0.5%SDS was preferred and in that medium,the dissolution profiles and saturation solubility of CXB-Poloxamer188-Aerosil at different ratios were investigated.Finally,based on the results,CXB-Poloxamer188-Aerosil achieved best performance at the ratio of 1?5?1.The optimized CXB solid dispersion was characterized by XRD,DSC,SEM,TGA and FT-IR,as well as stability tests and pharmacokinetic study.The DSC and XRD showed that the CXB was transferred into amorphous state and the TGA showed that the prepared solid dispersion was more thermal stable than API.The FT-IR gave a hint that there was intermolecular interaction between drug and polymers in the solid dispersion.Moreover,stability tests exhibited the good stability of the optimized CXB solid dispersion.As in the pharmacokinetic study,the C_max and AUC_0-24h of solid dispersion were 13.35±1.41?g/mL,81.84±9.75?g·h/mL respectively,which showed the great enhancement over the API.