A combined experimental and modeling approach to study the effects of high-shear wet granulation process parameters on granule characteristics.
The purpose of the current work is to study the effects of high-shear wet granulation process parameters on granule characteristics using both experimental and modeling techniques. A full factorial design of experiments was conducted on three process parameters: water amount, impeller speed and wet massing time. Statistical analysis showed that the water amount has the largest impact on the granule characteristics, and that the effect of other process variables was more pronounced at higher water amount. At high water amounts, an increase in impeller speed and/or wet massing time showed a decrease in granule porosity and compactability. A strong correlation between granule porosity and compactability was observed. A three-dimensional population balance model which considers agglomeration and consolidation was employed to model the granulation process. The model was calibrated using the particle size distribution from an experimental batch to ensure a good match between the simulated and experimental particle size distribution. The particle size distribution of three other batches were predicted, each of which was manufactured under different process parameters (water amount, impeller speed and wet massing time). The model was able to capture and predict successfully the shifts in granule particle size distribution with changes in these process parameters.
Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, NJ 08901, USA. preetanshu.pandey@bms.com
Preetanshu
P
Pandey
Jing
J
Tao
Anwesha
A
Chaudhury
Rohit
R
Ramachandran
Julia Z
JZ
Gao
Dilbir S
DS
Bindra
D002482:Cellulose / Q000737:chemistry; D004304:Dosage Forms; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry; D008956:Models, Chemical; D010316:Particle Size; D016062:Porosity; D013607:Tablets; D013997:Time Factors; D014867:Water / Q000737:chemistry*
D004304:Dosage Forms; D005079:Excipients; D013607:Tablets; D014867:Water; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose