Applicability of image analysis to support QbD driven development of pellets

Abstract

Objective

The stages of preparing high drug loaded pellets were investigated using static and dynamic imaging techniques to provide a greater understanding and ease the scale up process.

Significance

An example of a real case laboratory and production scale quality by design (QbD) based development of pellets is demonstrated. Potential process analytical technology (PAT) approaches by dynamic image analysis (DIA) are presented in various process phases.

Methods

Pellets were prepared at laboratory and production scale (high shear granulation, extrusion/spheronization, drying, and coating). The influence of process parameters on pellet properties (aspect ratio (AR), yield, pellet size, and their distribution) was investigated using static and DIA. During coating, we focused on the coating thickness and identification of potential agglomeration.

Results and conclusion

The effects of kneading time, amount of water, extrusion screen plate (ESP) opening diameter and thickness on pellet properties were confirmed in accordance with literature. In terms of screw speed, spheronization speed and time, no considerable influence on pellet properties was observed in the range of studied process parameters, thereby confirming the design space. In addition to the ESP thickness and opening diameter, quality of the ESP impacts the pellet properties. Lastly, coating thickness measurements with dynamic and static image analysis were comparable and an exemplary case of in-line agglomeration detection was presented. Real-time evaluation with PATVIS APA is an effective PAT tool for the evaluation of spheronization (pellet size distribution, AR, and yield) and coating (coating thickness, agglomeration detection).

Keywords:

• Extrusion/spheronization
• fluid bed pellet coating
• dynamic image analysis
• pellets
• particle size analysis

Acknowledgements

The authors express special thanks to all coworkers from Lek Pharmaceuticals d.d., who contributed to this study. Moreover, special thanks to Luka Peternel, for his support.

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

The authors are also thankful to Lek Pharmaceuticals d.d. for financial support and materials supplied for this study.