ENHANCEMENT OF DISSOLUTION AND BIOAVAILABILITY OF EZETIMIBE BY SPRAY DRIED MICROPARTICLES USING HP-β- CYCLODEXTRIN POLYMER

Objective: Enhancement of oral bioavailability of poorly water soluble drugs is the most challenging aspects of drug development. It is very important to find appropriate formulation approaches to improve the aqueous solubility and bioavailability of poorly aqueous soluble drugs. Ezetimibe is a new lipid lowering agent in the management of hyper-cholesterolemia. The drug is water-insoluble, lipophilic, and highly permeable. Therefore, bioavailability of ezetimibe may be improved by increasing its solubility. Method: The aim of the present study was to improve the solubility and dissolution rate of Ezetimibe by preparing microspheres by spray drying technique using HP β-cyclodextrin. Ezetimibe microspheres containing different ratios of HP- β-cyclodextrin were produced by using Propanol and water (50:50) as a solvent system. The prepared formulations containing different ratios of Ezetimibe and HP β-cyclodextrinwere evaluated for solubility and in-vitro dissolution. The prepared formulations were characterized by differential scanning calorimetry (DSC), X-ray diffraction spectroscopy (XRD), fourier transform infra-red spectroscopy (FTIR) and scanning electron microscopy (SEM). Dissolution profile of the prepared spray dried microspheres was compared with its physical mixture and pure sample. Result: Spray dried microspheres exhibited decreased crystallinity. The solubility of microspheres containing Ezetimibe and HP-β-cyclodextrin (1:3w/w) exhibited tenfold increases  and dissolution of same ratio microsphere showed 99% release in 20 min while same composition in physical mixture showed 37% release in 20 min. Consequently, from the above result it can be concluded that spray dried microspheres of Ezetimibe is a useful technique to improve the solubility and dissolution of poor water soluble drug like Ezetimibe.