title: On-line monitoring of fluid bed granulation by photometric imaging.
abstract: This paper introduces and discusses a photometric surface imaging approach for on-line monitoring of fluid bed granulation. Five granule batches consisting of paracetamol and varying amounts of lactose and microcrystalline cellulose were manufactured with an instrumented fluid bed granulator. Photometric images and NIR spectra were continuously captured on-line and particle size information was extracted from them. Also key process parameters were recorded. The images provided direct real-time information on the growth, attrition and packing behaviour of the batches. Moreover, decreasing image brightness in the drying phase was found to indicate granule drying. The changes observed in the image data were also linked to the moisture and temperature profiles of the processes. Combined with complementary process analytical tools, photometric imaging opens up possibilities for improved real-time evaluation fluid bed granulation. Furthermore, images can give valuable insight into the behaviour of excipients or formulations during product development.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Electronic address: ira.soppela@helsinki.fi.
authors.forename: Ira
authors.initials: I
authors.lastname: Soppela
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Osmo
authors.initials: O
authors.lastname: Antikainen
authors.affiliation: Pharmaceutical Sciences Laboratory, Department of Biosciences, Abo Akademi University, Turku, Finland.
authors.forename: Niklas
authors.initials: N
authors.lastname: Sandler
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Yliruusi
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D010316:Particle Size; D010783:Photometry / Q000295:instrumentation / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods
keywords: Fluid bed granulation; Image analysis; On-line monitoring; Photometric imaging; Powder processing; Process analytical technology