Melt granulation of pharmaceutical powders: a comparison of high-shear mixer and fluidised bed processes.

Abstract The main aim of this research was to compare in situ melt granulation process in high-shear mixers and fluidised bed equipments with particular attention to the final properties of granules. In addition, the study evaluated the suitability of melt granulation in fluidised bed for improving the dissolution rate of drugs. Agglomerates having identical composition (10%, w/w, of ibuprofen or ketoprofen, 20%, w/w, of PEG 6000 and 70%, w/w, of lactose monohydrate) were produced using both equipments and their morphology, particle size, flowability, friability, drug loading, dissolution behaviors at pH 1.2 and 7.4 and physicochemical properties (DSC and XRD analysis) have been evaluated and compared. The results showed that melt granulation can be successfully performed in both granulators. The utilization of a different equipment had strong impact on the particle size distribution of the granules and on their morphology, while the effect on others physical properties was little, as all the granules possess low friability and excellent flowability. Moreover both the solid state characteristics of the products and the dissolution behaviors of ibuprofen and ketoprofen granules were found to be practically independent of the equipment and all granules showed a significant increase of the drug dissolution rate in acidic conditions. In conclusion in situ melt granulation in fluidised beds could be considered a suitable alternative to the melt granulation in high-shear mixers.