title: Evolution of granule structure and drug content during fluidized bed granulation by X-ray microtomography and confocal Raman spectroscopy.
abstract: The distribution of the drug in the granular end product is a critical quality attribute in fluidized bed spray granulation of pharmaceuticals. The evolution of drug content inhomogeneity in a case study was examined as a function of granulation time. Intragranular structure was also investigated using confocal Raman spectroscopy and computerized X-ray microtomography. A principal component analysis was conducted on the results to investigate granule structure-drug content relationships. Inhomogeneity increased at the beginning of the process but later it was found to decrease. Changes in the homogeneity were accompanied by significant changes in the intragranular structure. It was concluded that segregation of the primary components explained the observed inhomogeneity at low saturation levels when the granules grow by layering, but at elevated moisture levels, granule growth is mediated by the coalescence of agglomerates, which promotes homogeneous distribution of the drug particles.
authors.affiliation: School of Pharmacy, University of Eastern Finland, FIN-70211 Kuopio, Finland. sami.poutiainen@uef.fi
authors.forename: Sami
authors.initials: S
authors.lastname: Poutiainen
authors.forename: Jari
authors.initials: J
authors.lastname: Pajander
authors.forename: Armi
authors.initials: A
authors.lastname: Savolainen
authors.forename: Jarkko
authors.initials: J
authors.lastname: Ketolainen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
mesh_terms: D004339:Drug Compounding; D015394:Molecular Structure; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D025341:Principal Component Analysis; D013059:Spectrum Analysis, Raman / Q000379:methods*; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations