371193 Scale-up Strategies of High Shear Wet Granulation of a 50% Drug Load Compound: From 60L Bottom-Driven Granulator to 600L Top-Driven Granulator

Wednesday, November 19, 2014
Galleria Exhibit Hall (Hilton Atlanta)
Jennifer (Ho) Sun, Pharmaceutical Commercialization Technology, Merck & Co., Inc., Summit, NJ; Merck Manufacturing Division, Merck & Co., West Point, PA, Mehrdad Kheiripour, Pharmaceutical Commercialization Technology, Merck&Co., Inc., West Point, PA and W. Mark Eickhoff, Pharmaceutical Commercialization Technology, Merck & Co., Inc., West Point, PA

We describe different strategies used for robust scale-up of a 50% drug load compound from a small scale bottom-driven granulator (60L Diosna) to a large scale top-driven granulator (600L Vector).

A 23 factorial design of experiments was conducted in bottom-driven 60L Diosna granulator, and a granule quality attribute design space was established.  Initial studies conducted for transfering a 60L bottom-driven Diosna process to a 75L top-driven Vector granulator revealed that differences in the granulator bowl and impeller blade geometry required increasing the shear flow (impeller speed) in the top-driven granulator in order to match the granule/tablet attributes.  Scale up of the process to a 600L top driven Vector granulator showed that the granulation end point was achieved with a longer wet massing time and with an impeller speed calculated using constant Froude number rule (N1   D10.5=N2D20.5 ; N and D are impeller speed and blade diameter respectively).  A longer granulation time for a larger vessel was suggested by Nakamura et. al.1who showed that in order to have dynamic similarity between the scales the granulation time should be adjusted such that the cumulative particle collision energy can be maintained at different scales. Alternatively, an increase in granulation fluid level was found to be a possible route for matching granule and tablet attributes across scales when impeller speed and granulation time are constrained from further increase. 

1: H. Nakamura, H. Fujii, S. Watano, "Scale-up of high shear mixer-granulator based on discrete element analysis", Powder Tech. 236, 149-156 (2013).

Extended Abstract: File Not Uploaded
See more of this Session: Poster Session: Pharmaceutical
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division