ABSTRACT:
Various techniques have been adopted for the improvement of solubility properties of poorly water- soluble drugs. Physical transformation is one of the promising approaches for improving solubility and dissolution rate of such drugs. Though the amorphous polymorph exhibits better biopharmaceutical properties, it is metastable and tends to revert back with time to thermodynamically more stable crystalline state. That is, stabilization of an amorphous form of poorly water- soluble drugs is another challenge in the formulation development of such drugs. The present study was aimed at preparation of solid dispersions of poorly water- soluble drug, etoricoxib using non- ionic surfactants as poloxamers by spray drying technique and to characterize the solid dispersions thus prepared by Infrared spectroscopy, dissolution studies, Differential Scanning Calorimetry, Thermo-gravimetric analysis, X-Ray Powder Diffraction and Scanning Electron Microscopy. Appearance of solid dispersions like matrix of near- spherical microparticles indicated presence of amorphous form of etoricoxib in solid dispersions. Absence of etoricoxib endotherm in DSC thermograms of solid dispersions suggested physical transformation of crystalline etoricoxib, which was confirmed by significantly decreased intensity of etoricoxib peaks in XRPD profiles of solid dispersions. Dissolution studies showed a significant enhancement in solubility characteristics of drug in solid dispersions as compared to pure etoricoxib and spray-dried etoricoxib. During stability testing, the optimized proportions of solid dispersions reported only an insignificant decrease in solubility characteristics of drug, but the saturation solubility and dissolution rate of spray- dried etoricoxib dropped drastically. Poloxamer-188 and poloxamer-407 were equally efficient in retaining the drug in its amorphous form. The study thus reveals tremendous potential of solid dispersions of drug with poloxamers to enhance its solubility.