DEVELOPMENT AND OPTIMIZATION OF SPRAY DRIED AMORPHOUS TERNARY SYSTEM OF CELECOXIB USING DESIGN OF EXPERIMENTS

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 spray drying method was employed to prepare CLX: PVP K30:HPB (hydroxypropyl β-cyclodextrin) amorphous ternary system (ATS). Statistical experimental design was employed to investigate the combined effect of two experimental factors, i.e., % of polyvinayl pyrrolidone (PVP) K30 and % of HPB on saturation solubility (SS), dissolution efficiency (DE) and mean dissolution time (MDT), considered as the responses to be optimized. 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. Central composite design allowed for defining a design space. Desirability function was used to attain simultaneous optimization of all responses. The desired goals were achieved for SS, DE and MDT. Experimental values obtained from the optimized formulations were very close to the predicted values, thus confirming the validity of the generated mathematical model. These results demonstrated the effectiveness of the proposed jointed use of PVP K30 and HPB, as well as the usefulness of the multivariate approach for the preparation of ATS. Validated optimum ATS were characterized by DSC, XRD, SEM and particle size analysis. Characterization results confirmed the formation of amorphous ternary system with average particle size 727.9±260.6nm.