Effect of process parameters on compressibility of granulation manufactured in a high-shear mixer

Various processing variables that can influence granulation characteristics of a lactose-based formulation were evaluated using a Plackett-Burman expe rimental design. These parameters were impeller speed, granulating solution addition rate, total amount of water added in the granulation step. wet ma ssing time, moisture content of the granulation after drying, and screen si ze used for the dry milling. Results showed that granulation growth was enh anced by the increase in the amount of added water, high impeller speed. an d short wet massing time. On the other hand, moisture content had the large st impact on granulation compressibility, followed by the wet massing time and impeller speed. Increasing moisture content of the granulation and decr easing wet massing time or impeller speed increased granulation compressibi lity. Increasing impeller speed and/or wet massing time decreased granule p orosity and fragmentation propensity, which led to decreased granulation co mpressibility. Granulation compressibility was extremely sensitive to proce ssing conditions. Tablets from all runs showed acceptable weight variation and friability, suggesting that the parameters evaluated had little effect on these responses in the ranges tested. (C) 2000 DuPont Pharmaceutical Com pany. Published by Elsevier Science B.V. All rights reserved.