Granule characterization during fluid bed drying by development of a near infrared method to determine water content and median granule size.
OBJECTIVE
Water content and granule size are recognized as critical process and product quality parameters during drying. The purpose of this study was to enlighten the granule behavior during fluid bed drying by monitoring the major events i.e. changes in water content and granule size.


METHODS
NIR spectra collected during drying and water content of sampled granules were correlated by principal component analysis (PCA) and partial least squares regression (PLSR). NIR spectra of dried granules were correlated to median granule size in a second PCA and PLSR.


RESULTS
The NIR water model discriminates between various stages in fluid-bed drying. The water content can be continuously predicted with errors comparable to the reference method. The four PLS factors of the granule size model are related to primary particle size of lactose, median granule size exceeding primary particle size and amorphous content of granules. The small prediction errors enable size discrimination between fines and granules.


CONCLUSIONS
For product quality reasons, discrimination between drying stages and end-point monitoring is highly important. Together with the possibilities to determine median granule size and to distinguish fines this approach provides a tool to design an optimal drying process.
Nieuwmeyer
Florentine J S
FJ
Department of Pharmaceutics, NV Organon, P.O. Box 20, 5340 BH, Oss, The Netherlands. Florentine.nieuwmeyer@organon.com
Damen
Michiel
M
Gerich
Ad
A
Rusmini
Federica
F
van der Voort Maarschalk
Kees
K
Vromans
Herman
H
D003890:Desiccation; D005079:Excipients / Q000737:chemistry* / Q000592:standards; D007785:Lactose / Q000737:chemistry* / Q000592:standards; D016018:Least-Squares Analysis; D008956:Models, Chemical; D010316:Particle Size; D011208:Powders; D025341:Principal Component Analysis; D011786:Quality Control; D019265:Spectroscopy, Near-Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000032:analysis*
D005079:Excipients; D011208:Powders; D014867:Water; D007785:Lactose