Prospective Validation of High-Shear Wet Granulation Process by Wet Granule Sieving Method. I. Selection and Characterization of Sieving Parameters for Wet Granules

To characterize the progression of high-shear wet granulation for various drugs and formulations based on the particle size distribution of wet granules during granulation, a general sieving method for wet granules was investigated. 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). Because of its small size and efficient sifting mechanism, a sonic sifter was used to determine the wet granulation particle size distribution. From the good correlation of particle size distribution between wet granules and dry-sized granules, an intensity of 80% of full-scale amplitude and a sieving time of 3 min were selected as wet granule sieving parameters. 7% general sieving method showed good measurement precision as long as the determination was completed within 20 min after sampling, Further, the method was independent of sampling position within the mixer chamber.