Prospective Validation of High-Shear Wet Granulation Process by Wet Granule Sieving Method. II. Utility of Wet Granule Sieving Method

Abstract

The general utility of a method for determination of high-shear wet granulation end point by monitoring the wet granule particle size distribution was evaluated. Wet granulation was conducted in a 25-liter high-shear mixer using four model drugs with different solubilities and particle sizes (ethenzamide, unmilled and milled acetaminophen, and antipyrine). For each drug formulation, its wet granule particle size fraction and target range for granulation end point determination were selected based on the tablet characteristics that are known to be influenced by the wet granulation process. Granules manufactured under different conditions (i.e., different main and chopper blade speeds and binder supplying rate) but manufactured to the same granulation end point determined by the selected fraction and range showed very similar granule characteristics and subsequently very similar tabler characteristics. From the fact that there was a good correlation between the wet and dry-sized granule particle size distributions even if the drying method was changed from fluid-bed drying to vacuum drying, the general application of the end point determining method was verified. Further, the method was shown to be sensitive to the critical granulation parameters for granulation progression and to be very capable of determining the granulation extent. Thus, it was suggested that the method is applicable to various drugs and formulations for determination of wet granulation end point.