Abstract

PREPARATION AND CHARACTERIZATION OF EZETIMIBE FREEZE-DRIED TABLETS USING ZYDIS® TECHNOLOGY

Safaa A. Kadhim, Asst. Prof Dr. Shaimaa Nazar*, Prof. Dr. Alaa A. Abdul Rasool

Abstract

The aim of this study is to prepare and characterize ezetimibe as freeze dried tablets using Zydis technology. Ezetimibe is a poorly watersoluble drug which is one of the lipid lowering drugs that selectively inhibit the intestinal absorption of cholesterol and related phytosterols prepared as freeze dried tablets in order to improve its solubility and dissolution rate. Different formulas were prepared and different binding agents were used with different concentrations such as gelatin, Xanthan gum, Dextrin, and Microcrystalline cellulose. Gelatin was found to be the best one according to the results. The bulking agent (mannitol) and glycine also used in different concentrations in order to optimize the best formulation. The best formula (EZT-F2) was prepared by dispersing ezitimibe in aqueous solution of gelatin (2.5% w/v), glycine (1% w/v), and mannitol (2% w/v). The tablets were evaluated for weight variation, wetting time, disintegration time, and content uniformity, and the best formulations were evaluated for in vitro dissolution rate. Amongst all formulas, formula EZT-F2 (F5+drug) was found to be the best formula with a disintegration time of 4 ±1.5 sec. and % drug release of 79.7% ± 1.54 after 7 min which is similarly closed to the results of the marketed tablet; Ezetrol® that contains several superdisintegrants and surfactants in its formulation with percent drug release 82.64 ± 1.82 after 7 min. The stability of the prepared tablet was studied by storing the prepared ezitimibe freeze dried tablets at 40, 50 and 60oC for four months. The estimated expiration date at 25oC was approximately 2.187 years. On the other hand, the accelerated stability study at 40±2oC/ 75±5 % RH of this formula for three months showed no significant changes (p

Keywords: ezetimibe, fast dissolving tablets, freeze drying technique.