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.

Optimization Study of Aqueous Film-Coating Process in the Industrial Scale Using Design of Experiments

“…This explains the negative effect of the spray rate on the disintegration time. The negative effect of the spray rate on hardness has also been established in other studies [7,17].…”

“…The observed positive effect of the inlet air temperature on the disintegration time can be explained as the increase in temperature is affecting the amount of moisture removed during the process. In the study by Teżyk et al [17] it was revealed that inlet air temperature is a significant factor for the hardness of film-coated tablets [17]. In the mentioned study, and also, in the study by Teckoe et al [16] the tested coating parameters didn't show a significant effect on the disintegration time.…”