title: Process Analytical Technology for High Shear Wet Granulation: Wet Mass Consistency Reported by In-Line Drag Flow Force Sensor Is Consistent With Powder Rheology Measured by At-Line FT4 Powder Rheometer.
abstract: Drag flow force (DFF) sensor that measures the force exerted by wet mass in a granulator on a thin cylindrical probe was shown as a promising process analytical technology for real-time in-line high-resolution monitoring of wet mass consistency during high shear wet granulation. Our previous studies indicated that this process analytical technology tool could be correlated to granulation end point established independently through drug product critical quality attributes. In this study, the measurements of flow force by a DFF sensor, taken during wet granulation of 3 placebo formulations with different binder content, are compared with concurrent at line FT4 Powder Rheometer characterization of wet granules collected at different time points of the processing. The wet mass consistency measured by the DFF sensor correlated well with the granulation's resistance to flow and interparticulate interactions as measured by FT4 Powder Rheometer. This indicated that the force pulse magnitude measured by the DFF sensor was indicative of fundamental material properties (e.g., shear viscosity and granule size/density), as they were changing during the granulation process. These studies indicate that DFF sensor can be a valuable tool for wet granulation formulation and process development and scale up, as well as for routine monitoring and control during manufacturing.
authors: Bristol-Myers Squibb, Co., New Brunswick, New Jersey 08903. Electronic address: Ajit.Narang@bms.com.
authors: Ajit S
authors: AS
authors: Narang
authors: Lenterra, Inc., Newark, New Jersey 07103. Electronic address: Sheverev@Lenterra.com.
authors: Valery
authors: V
authors: Sheverev
authors: Freeman Technology, Miller Court, Tewkesbury Business Park, Severn Dr, Tewkesbury, Gloucestershire GL20 8DN, UK. Electronic address: Tim.Freeman@FreemanTech.co.uk.
authors: Tim
authors: T
authors: Freeman
authors: Bristol-Myers Squibb, Co., New Brunswick, New Jersey 08903.
authors: Douglas
authors: D
authors: Both
authors: Lenterra, Inc., Newark, New Jersey 07103.
authors: Vadim
authors: V
authors: Stepaniuk
authors: Freeman Technology, Miller Court, Tewkesbury Business Park, Severn Dr, Tewkesbury, Gloucestershire GL20 8DN, UK.
authors: Michael
authors: M
authors: Delancy
authors: Freeman Technology, Miller Court, Tewkesbury Business Park, Severn Dr, Tewkesbury, Gloucestershire GL20 8DN, UK.
authors: Doug
authors: D
authors: Millington-Smith
authors: Bristol-Myers Squibb, Co., New Brunswick, New Jersey 08903.
authors: Kevin
authors: K
authors: Macias
authors: Bristol-Myers Squibb, Co., New Brunswick, New Jersey 08903.
authors: Ganeshkumar
authors: G
authors: Subramanian
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D010919:Placebos; D011208:Powders; D012212:Rheology; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D010919:Placebos; D011208:Powders; D013607:Tablets; D002482:Cellulose; C008079:hydroxypropylcellulose; D007785:Lactose; D002266:Carboxymethylcellulose Sodium; C109691:microcrystalline cellulose
keywords: DFF sensor; FT4 Powder Rheometer(®); formulation; granulation; high shear wet granulation; high throughput technologies; powder technology; process analytical technologies; processing; unit operations