Formulation and Evaluation of Ezetimibe Lyophilized Dry Emulsion Tablets

摘要

This article presents the development of lyophilized dry emulsion tablets prepared with the dry emulsion technique to enhance the in-vitro dissolution and in-vivo performance of the poorly bioavailable drug Ezetimibe. Ezetimibe (EZT) is a lipid-lowering drug that inhibits intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients. Ezetimibe has a very low solubility and dissolution rate resulting in highly variable bioavailability, which is also in part due to extensive efflux by p-glycoprotein (P-Gp). Tablets were fabricated by freezedrying o/w emulsions of Ezetimibe. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol), as the water phase and Labrafac? as the oil phase under proper homogenization. In the present study friability, disintegration time, and in-vitro dissolution of lyophilized dry emulsion tablets were done. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In-vitro dissolution studies revealed the enhanced dissolution rate of Ezetimibe from the lyophilized tablets compared to the plain drug. DSC studies proved presence of the drug in the amorphous form in the fabricated tablets. The obtained results suggest a promising, easy-to-manufacture and effective dosage form for the treatment of hyperlipidemia. Keywords: Ezetimibe, lyophilized dry emulsion tablet, and hyperlipidemia, freeze drying, Labrafac.