Preparation and characterisation of ibuprofen–poloxamer 188 granules obtained by melt granulation

Abstract

The aim of this study was to prepare, by melt granulation, granules containing ibuprofen as a poorly water soluble model drug in order to improve its dissolution rate and its availability; lactose as a diluent and poloxamer 188 (Lutrol ® F68), as a new meltable hydrophilic binder, were used. The granules were prepared in a laboratory-scale high-shear mixer, using a jacket temperature of 50°C and an impeller speed of 500 rpm. The particle size analysis shows that the main fraction was between 200 and 500 μm, while the determination of drug content indicated that ibuprofen was quite uniformly distributed in all the fractions. Scanning Electron Microscopy (SEM), image and fractal analysis revealed that the granules did not have a perfect spherical shape and a rugged surface ( D s=2.6475). The in vitro dissolution tests showed an increase in the dissolution rate of granules compared to pure drug and physical mixture. The characterisation of the samples, performed by Differential Scanning Calorimetry (DSC) and X-ray powder diffraction (XRD), suggests that the improvement of dissolution rate could be correlated to the formation of a eutectic mixture between the drug and the binder. Stability studies indicated that the granule properties do not change, at least after 1 year of storage at 25°C. In conclusion, the results of this work suggest that the melt granulation technique is an easy and fast method to improve the dissolution rate of ibuprofen, using poloxamer 188 as a new hydrophilic meltable binder.