title: Combining microwave resonance technology to multivariate data analysis as a novel PAT tool to improve process understanding in fluid bed granulation.
abstract: A set of 192 fluid bed granulation batches at industrial scale were in-line monitored using microwave resonance technology (MRT) to determine moisture, temperature and density of the granules. Multivariate data analysis techniques such as multiway partial least squares (PLS), multiway principal component analysis (PCA) and multivariate batch control charts were applied onto collected batch data sets. The combination of all these techniques, along with off-line particle size measurements, led to significantly increased process understanding. A seasonality effect could be put into evidence that impacted further processing through its influence on the final granule size. Moreover, it was demonstrated by means of a PLS that a relation between the particle size and the MRT measurements can be quantitatively defined, highlighting a potential ability of the MRT sensor to predict information about the final granule size. This study has contributed to improve a fluid bed granulation process, and the process knowledge obtained shows that the product quality can be built in process design, following Quality by Design (QbD) and Process Analytical Technology (PAT) principles.
authors.affiliation: Institute of Biotechnology and Bioengineering, IST, Technical University of Lisbon, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Lourenço
authors.forename: Thorsten
authors.initials: T
authors.lastname: Herdling
authors.forename: Gabriele
authors.initials: G
authors.lastname: Reich
authors.forename: José C
authors.initials: JC
authors.lastname: Menezes
authors.forename: Dirk
authors.initials: D
authors.lastname: Lochmann
mesh_terms: D004339:Drug Compounding / Q000379:methods* / Q000706:statistics & numerical data; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D006813:Humidity; D016018:Least-Squares Analysis; D008872:Microwaves; D015999:Multivariate Analysis; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D025341:Principal Component Analysis; D017064:Process Assessment, Health Care / Q000379:methods*; D011786:Quality Control; D013678:Technology, Pharmaceutical / Q000379:methods / Q000706:statistics & numerical data; D013696:Temperature
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations