Application of Quality by Design Concepts in the Development of Fluidized Bed Granulation and Tableting Processes

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 gr...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2013-06, Vol.102 (6), p.1869-1882
Main Authors: Djuris, Jelena, Medarevic, Djordje, Krstic, Marko, Djuric, Zorica, Ibric, Svetlana
Format: Article
Language:English
Subjects:
Acetaminophen - administration & dosage
Acetaminophen - chemistry
Analgesics, Non-Narcotic - administration & dosage
Analgesics, Non-Narcotic - chemistry
Delayed-Action Preparations - chemistry
dissolution rate
Drug Compounding - methods
factorial design
fluid bed
granulation
Least-Squares Analysis
Multivariate Analysis
partial least squares
Particle Size
Polyethylene Glycols - chemistry
Principal Component Analysis
regulatory science
Solubility
tableting
Tablets
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Summary: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.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.23530