In situ fluidized hot melt granulation using a novel meltable binder: Effect of formulation variables on granule characteristics and controlled release tablets

Abstract

In situ fluidized hot melt granulation (FHMG) for different (ternary) formulations based on glyceryl palmito-stearate as non-conventional meltable binder and ibuprofen as model drug was examined for controlled release applications. The process was robust, lasted only 15min, and enabled to attain high yields (95–98wt.%). The obtained granules presented a bimodal size distribution, having the major mode of 200μm and good flow properties, thus avoiding the necessity to add other lubricants for tablet compaction. The crystalline structure of ibuprofen and of the non meltable excipients was retained, and that of glyceryl palmito-stearate was recovered in the final granules. The resulting ibuprofen tablets had good pharmacotechnical properties. The granulation process did not modify release profiles from the tablets. The main factor influencing the release profiles was the content of glyceryl palmito-stearate in the formulations. A high drug load (50wt.%), which is particularly important in the case of high dose active pharmaceutical ingredients, was achieved. Glyceryl palmito-stearate performed a triple function in the tablet formulation: as a meltable binder, as a controlled release matrix and as a lubricant.