“CENTRAL COMPOSITE DESIGN TO ENHANCE THE SOLUBILITY OF CELECOXIB”

Y. D. Pawar*, K. B. Patil and P. D. Chaudhrari

ABSTRACT

One of the major challenges in pharmaceutical development is the poor dissolution performance of drugs. Celecoxib (CLX) is a poorly water soluble drug with its bioavailability being limited by its poor dissolution. In this study solvent evaporation method by rota evaporator was employed to prepare solid dispersion drug and polymers. Central composite design employed statistical experimental design tool and investigated the combined effect of experimental factors, i.e., % of PVP K30, PVP K90 and % of β-cyclodextrin (BCD) on responses like saturation solubility (SS), dissolution efficiency (DE) and mean dissolution time (MDT). Dissolution profile of physical mixture of drug and polymers was performed, and results so obtained were compare with the results of solid dispersion prepared by solvent evaporation technique. Design of experiment was used in the context of quality by design, which requires a multivariate approach for understanding the multifactorial relationships among experimental factors. Desirability function was used to attain optimization of responses. The theoretical desired goals were not achieved for SS, DE and MDT using drug or physical mixtures, and therefore there was a need of highly efficient technique like solvent evaporation. Predicted values were very close to the experimental values obtained from the optimized formulation, thus it confirmed that the generated mathematical model was valid. Results of dissolution study showed that PVP K30 increases more solubility compare to PVP K90. The results demonstrated the effect of the proposed combined use of BCD, PVP K90 and PVP K30. Validated optimized solid dispersion was characterized by DSC, XRD, SEM and particle size analysis. Characterization results confirmed the formation of partial amorphous drug complex with average particle size 1703.1±996.3 nm.

Keywords: Celecoxib, PVP K30, ?-cyclodextrin, solid dispersion, PVP K90.