Investigation of various practical techniques to enhance dissolution of ezetimibe from oral tablets: A comparative study

Objective: The aim of this work was to investigate and compare various practical techniques to enhance dissolution of ezetimibe, a class II BCS compound. Ezetimibe is a poorly soluble compound with variable oral bioavailability. Nanosuspensions, hydroxypropylβcyclodextrin (HPβCD) complexes as well as combination of surfactant were techniques investigated. Methods: Nanosuspension of ezetimibe was prepared using solventantisolvent precipitation technique. The nanosuspensions were characterized by powder x-ray diffractometry and scanning electron microscopy. HPβCD inclusion complexes were prepared using physical mixture, coevaporation and kneading methods. These complexes were characterized by fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Ezetimibe tablet formulations containing drug nanosuspensions, HPβCD complexes as well as sodium lauryl sulphate (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.

Keywords: Ezetimibe ; Nanosuspension ; HP-ß Cyclodextrin complexes ; SLS ; Nanosuspension tablets ; Drug-SLS tablets .