Study growth kinetics in fluidized bed granulation with at-line FBRM.
In this study, a novel at-line focused beam reflectance measurement (FBRM) technique was developed to investigate granule growth in a fluidized bed granulation (FBG). The chord length distribution (CLD) measured by the FBRM was used to represent granule particle size distribution (PSD). Through a systematic study, it was proved that the trends of the chord length measured by the at-line FBRM technique were identical to those measured by a laser diffraction instrument and sieve analysis in spite of different measurement mechanisms. The portable at-line FBRM technique was successfully applied to a granule growth kinetics study for a fluidized bed granulation performed in a Glatt GPCG-1 granulator. Granule size evolution was clearly exhibited by the at-line FBRM. Spray rate was found to be the most significant factor on the granule growth compared with the other two factors: binder solution concentration and intra- to extra-granular microcrystalline cellulose (MCC) ratio for the formulation studied in this work. The CLD evolution measured by the FBRM confirmed that the granule agglomeration was mainly dominated by the binder on the granule surface. The at-line FBRM enables us to select appropriate process parameters and effectively control the fluid bed granulation process.
Hu
Xinhui
X
Pharmaceutical Development, Johnson and Johnson Pharmaceutical Research and Development, Welsh and Mckean Roads, Spring House, PA 19477, USA. xhu10@prdus.jnj.com
Cunningham
John C
JC
Winstead
Denita
D
D002482:Cellulose / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D007700:Kinetics; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D012827:Silicone Oils / Q000737:chemistry
D005079:Excipients; D011208:Powders; D012827:Silicone Oils; D002482:Cellulose; C109691:microcrystalline cellulose