Objective:The objective of this study was to prepare and investigate better and stable amorphous ezetimibe nanosuspensions for oral bioavailability enhancement.Materials and Methods:Nanosuspensions of ezetimibe were prepared by solvent-antisolvent precipitation technique using the surfactant, Tween 80 as stabilizer. The nanosuspension preparation was optimized for particle size by investigating two factors that is, solvent:antisolvent ratio and surfactant concentration, at three levels. The formulations were characterized for particle size, surface morphology, crystallinity, zeta potential, saturation solubility, in vitro drug release and in vivo drug absorption.Results:The nanosuspensions of ezetimibe were successfully prepared using solvent-antisolvent precipitation. The two factors solvent:antisolvent ratio and surfactant concentration influenced the particle size of the nanosuspensions prepared. Nanosuspensions were smooth and spherical. The X-ray powdered diffraction and differential scanning calorimetry results indicated that the antisolvent-solvent method led to the amorphization of ezetimibe. Under storage, the amorphous ezetimibe nanosuspensions demonstrated significant physical stability. Ezetimibe nanosuspensions increased the saturation solubility to an extent of 4-times. Ezetimibe nanosuspensions completely dissolved in the dissolution medium within 1 h, while pure drug was dissolved up to 42% during same time. The Cmax with ezetimibe nanosuspension was approximately 3-fold higher when compared with that of ezetimibe conventional suspensions administered orally.Conclusions:Stable amorphous ezetimibe nanosuspensions were successfully prepared and these nanosuspensions demonstrated dramatic improvement in oral bioavailability of the active.

Objective: The aim of this work was to investigate and compare various practical techniques to enhance dissolution of ezetimibe, a Class II Biopharmaceutics Classifi cation System compound. Ezetimibe is a poorly soluble compound with variable oral bioavailability. Nanosuspensions, hydroxypropyl-beta-cyclodextrin (HPβCD) complexes as well as combination of surfactant were techniques investigated. Materials and Methods: Nanosuspension of ezetimibe was prepared using solvent-antisolvent precipitation technique. The nanosuspensions were characterized by powder X-ray diffractometry and scanning electron microscopy. HPβCD inclusion complexes were prepared using physical mixture, co-evaporation, and kneading methods. These complexes were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Ezetimibe tablet formulations containing drug nanosuspensions, HPβCD complexes as well as sodium lauryl sulfate (SLS) enrichment were prepared and evaluated for dissolution. Results and Discussion: Nanosuspensions of ezetimibe with a mean particle size of 900 nm were successfully prepared using solvent-antisolvent precipitation. FTIR and DSC studies confi rmed the formation of ezetimibe inclusion complexes. Tablets prepared using pure drug showed very poor dissolution. In contrast, tablets of nanosuspensions, HPβCD inclusion complexes and SLS mixtures showed enhanced dissolution. The tablets prepared using nanosuspensions demonstrated enhanced dissolution rate when compared to the formulations prepared using HPβCD complexes and SLS enrichment. All the techniques investigated can be used to enhance the dissolution of ezetimibe and thus can enhance the oral bioavailability and also reduce the fl uctuations in the oral bioavailability. Conclusion: The techniques that were employed in this present work, nanosuspensions seem to be better when compared to cyclodextrin inclusion complexes and SLS enrichment in enhancing solubility and dissolution rate of ezetimibe.