Senior Staff Pharmacologist US Food and Drug Administration Silver Spring, Maryland
Continuous twin-screw wet granulation is one of the emerging technologies for manufacturing solid oral dosage forms. Compared to batch operation, continuous manufacturing offers several advantages, including reduced processing time, uniform granule size distribution and shape, and real-time process control. Continuous granulation technologies have been successfully employed for the commercial manufacture of immediate-released tablets. However, the use of a high polymer loading in extended-release (ER) formulations has presented challenges in developing and operating within the desired design space. This is due to the limited range of options available for setting the screw configuration and operating within the appropriate process parameter ranges. The design space defines the flow dynamics within the barrel and plays a crucial role in determining the granule properties. Several factors may affect the yield of a twin-screw wet granulation process, such as the powder feeding rate, screw speed, and the number of kneading and sizing elements. The impact of these factors on the mean residence time (MRT), bulk, flow and dynamics properties of the granules, and the breaking strength and dissolution of tablets will be discussed in this presentation using a case study of metoprolol succinate ER tablets. Our results showed that screw design and processing parameters affected the MRT and the critical characteristics of granules and tablets. The screw speed had the most significant impact on MRT as well as granules and tablet characteristics. The granule characteristic mainly influenced the early phase of drug release of ER tablets, while the formulation attributes dominated the later phase of drug release. In conclusion, this study demonstrated that the screw configuration and process parameters should be considered to determine the optimum operating space for granulating ER formulations in a twin-screw wet granulation process.
Learning Objectives:
Upon completion, participants will be able to understand how the screw configuration parameters and operating conditions contribute to the critical characteristic of granules and tablets.
Upon completion, participants will understand the factors that governs the twin-screw wet granulation process dynamics for manufacturing ER tablets.
Upon completion, participants will be able to identify possible failure modes for the process.