A study on the effect of wet granulation on microcrystalline cellulose particle structure and performance.
OBJECTIVE
The aim of this study was to investigate the mechanism of the effect of wet granulation process on the compaction properties of microcrystalline cellulose (MCC).


METHODS
MCC alone and with hydroxypropyl cellulose (HPC) as a binder were wet granulated by a high-shear process using different granulation parameters (over- and undergranulated). Overgranulated batches were also ball milled after drying and compared to the unmilled material. MCC starting material and granulation were characterized for particle size distribution, surface area, porosity, and isothermal moisture uptake. Compaction behavior of the MCC and granulations was also studied using a compaction simulator.


RESULTS
In all cases, the wet granulation process decreased MCC primary particle porosity. Wet granulation also reduced compactibility of MCC to different degrees. Overgranulated batch with HPC showed the lowest compactibility and was less compactible than the batch without HPC granulated using the same parameters. Ball-milled material showed an increase in porosity and was significantly more compactible than the unmilled granulation from the same batch.


CONCLUSIONS
The decrease in MCC compactibility after granulation is associated with the decrease in MCC primary particle porosity and in some cases with the formation of large dense granules as well. Under certain conditions, milling seems to counteract the effect of wet granulation on MCC compactibility.
Badawy
Sherif I Farag
SI
Pharmaceutical Research Institute, Bristol-Myers Squibb Co., One Squibb Drive, New Brunswick, New Jersey, 08903, USA. sherif.badawy@bms.com
Gray
David B
DB
Hussain
Munir A
MA
D000327:Adsorption; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D009584:Nitrogen / Q000737:chemistry; D010316:Particle Size; D016062:Porosity; D013678:Technology, Pharmaceutical; D014867:Water / Q000737:chemistry
D014867:Water; D002482:Cellulose; C008079:hydroxypropylcellulose; D009584:Nitrogen