(343f) Advanced Manufacturing: Mechanistic Understanding and Optimization of a Twin-Screw Wet Granulation Process for Manufacturing of Extended-Release Tablets

Advanced manufacturing has the potential to revolutionize the pharmaceutical industry by enhancing drug quality, addressing shortages of medicines, and accelerating time-to-market. The U.S Food and Drug Administration (FDA) actively encourages the adoption of advanced technologies to ensure the safety and efficacy of drug products. Continuous manufacturing has emerged as a focal point due to its ability to seamless process scale-up, increase the production efficiency, and improve the process control. However, its successful implementation requires a comprehensive understanding of the process dynamic. Twin-screw wet granulation (TSWG) is a continuous manufacturing technology that may be implemented in a fully continuous from-powder-to-tablet production line. While successfully used in the commercial manufacture of immediate-released tablets; implementing TSWG for extended-release (ER) drug products has presented challenges due to the limited options for setting the design and operating parameters to processing the ER formulations. This presentation delves into a systematic approach for defining an optimal design space for TSWG processes, focusing on the interplay between design and operating parameters and their impact on process dynamic and critical characteristics of granules and ER tablets.

A case study involving the processing of an ER formulation with high load of swellable polymers is presented. Through a definitive screening design and principal component analysis, the influence of screw speed, powder feeding rate, and the number of kneading (KEs) and sizing elements on residence time distribution (RTD) parameters and granules and tablets characteristics was investigated. The results demonstrated that screw design and operating parameters affected the flow and bulk characteristics of granules, while the screw speed and KEs were the most significant factors affecting the RTD parameters. Dissolution profiles revealed that granule characteristics mainly influenced the early-phase drug release, while formulation matrix dominated the extended drug release phase. In summary, this presentation not only underscores the importance of simultaneous optimization of operating and design parameters for the manufacturing of ER tablets with desired performance characteristics, but also emphasizes in the notable failure modes in this process. Furthermore, strategies to incorporate quality-by-design principles to monitor and control the critical quality attributes of granules are discussed.

DISCLAIMER

This presentation reflects the views of the presenter and should not be construed to represent FDA’s views or policies.