Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets – a case study

Abstract

The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett–Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

Keywords:

• Dry granulation
• slugging
• coating
• process optimization
• Plackett–Burman
• full factorial design
• design space

Acknowledgments

The authors wish to gratefully acknowledge Grzegorz Harańczyk for statistical discussions and valuable input.

This work has been partially financed by Poznan University of Medical Sciences, Poland, grant No. 502-01-033-14–429-03439.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This work has been partially financed by Poznan University of Medical Sciences, Poland, grant No. 502-01-033-14–429-03439.