title: Application of quality by design concepts in the development of fluidized bed granulation and tableting processes.
abstract: This study illustrates the application of experimental design and multivariate data analysis in defining design space for granulation and tableting processes. According to the quality by design concepts, critical quality attributes (CQAs) of granules and tablets, as well as critical parameters of granulation and tableting processes, were identified and evaluated. Acetaminophen was used as the model drug, and one of the study aims was to investigate the possibility of the development of immediate- or extended-release acetaminophen tablets. Granulation experiments were performed in the fluid bed processor using polyethylene oxide polymer as a binder in the direct granulation method. Tablets were compressed in the laboratory excenter tablet press. The first set of experiments was organized according to Plackett-Burman design, followed by the full factorial experimental design. Principal component analysis and partial least squares regression were applied as the multivariate analysis techniques. By using these different methods, CQAs and process parameters were identified and quantified. Furthermore, an in-line method was developed to monitor the temperature during the fluidized bed granulation process, to foresee possible defects in granules CQAs. Various control strategies that are based on the process understanding and assure desired quality attributes of the product are proposed.
authors.affiliation: Department of Pharmaceutical Technology Faculty of Pharmacy, University of Belgrade Belgrade 11221 Serbia. Electronic address: jelena.djuris@pharmacy.bg.ac.rs.
authors.forename: Jelena
authors.initials: J
authors.lastname: Djuris
authors.affiliation: Department of Pharmaceutical Technology Faculty of Pharmacy, University of Belgrade Belgrade 11221 Serbia.
authors.forename: Djordje
authors.initials: D
authors.lastname: Medarevic
authors.affiliation: Department of Pharmaceutical Technology Faculty of Pharmacy, University of Belgrade Belgrade 11221 Serbia.
authors.forename: Marko
authors.initials: M
authors.lastname: Krstic
authors.affiliation: Department of Pharmaceutical Technology Faculty of Pharmacy, University of Belgrade Belgrade 11221 Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Djuric
authors.affiliation: Department of Pharmaceutical Technology Faculty of Pharmacy, University of Belgrade Belgrade 11221 Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ibric
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D016018:Least-Squares Analysis; D015999:Multivariate Analysis; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D025341:Principal Component Analysis; D012995:Solubility; D013607:Tablets
chemical_list: D018712:Analgesics, Non-Narcotic; D003692:Delayed-Action Preparations; D013607:Tablets; D000082:Acetaminophen; D011092:Polyethylene Glycols