(M0930-08-51) Peak Shear and the Effect of Kneading Block Geometries on Twin Screw Granulation Process Design

Purpose: Twin-Screw Melt Granulation (TSMG) is an emerging processing method which enables continuous processing of powder blends to improve properties. However, with materials that need to be granulated, processing on a twin-screw extruder (TSE) is sometimes a challenge. Peak shear is a known issue causing degradation and particle attrition of drug compounds. Peak shear is found at the overflight and direct intermesh of the twin screw element (figure 1) where the gap is lowest and tip velocities are highest. With consideration of other factors including screw design, overflight gaps, and throughput rate vs. screw rpm ratios, a system can be designed to minimize exposure to peak shear and create a robust process. In addition to peak shear, average shear throughout the screw, which occurs in the screw channels, and extensional mixing, which occurs in mixing zones, also can play a role in drug degradation.

Methods: Standard kneading block elements have a narrow overflight clearance of 0.1 mm typically in combination with a wider disk width of 5 mm (figure 2). These elements cause instances of elevated peak shear leading to drug degradation. Using a new design with larger overflight clearances (0.2, 0.3, and 0.4 mm) along with a narrower width disk of 2 and 4 mm (figure 3), the peak shear is reduced. An intermeshing ZSE 18 mm HP (co-rotating, 25:1 L/D, 3.2 cc/dia, 1.5 OD/ID) TSE was used to process a formulation of 80% lactose monohydrate (LAC, solid particles, placebo) and 20% hydroxypropyl-cellulose (HPC, Klucel™ ELF grade, binder) and a second formulation of 90% Pearlitol (Mannitol, solid particles, placebo) and 10% hydroxypropyl-cellulose (HPC, Klucel™ ELF grade, binder). Processing conditions (rate vs. rpm, screw design, and temperatures), and kneading block element geometries were varied to evaluate effects on granule formation and subsequent degradation and attrition of particles. Peak Shear was calculated through equation 1.

Results: With changes to screw design, overflight gaps, throughput rate vs. screw rpm, and processing temperatures, granule size and consistency was evaluated. A control (formula 1 and screw design 1, Figure 5) was used as a comparison using a previous study that implemented the standard kneading block design (1) that produced granules that were able to be consistently formed. However, the mean diameter of the LAC particles was reduced from 22.3 µm to 10 µm indicating degradation. The peak shear ranged from 942 – 2826 sec^-1 for the samples collected. Full processing results can be seen in table #1. With the new kneading block design, implemented in screw #2 (figure 6), initial results with processing conditions comparable to screw #1 caused practically no granule formation, with only powder able to be produced (2). The main factor was seemingly the reduction in shear at the kneading blocks due to the the modified elements. The peak shear was reduced from 942 sec^-1 to 471 sec^-1, 314 sec^-1, and 236 sec^-1, (based on 100 rpm at the respective overflight gap of 0.2, 0.3, and 0.4 mm chosen). Several processing changes were made to increase and influence the granule growth. The stagger angle, the angle between each block in the set of kneading blocks, was set at 60° and 90° to increase the energy input and residence time. The degree of fill was also increased (high rate vs. low rpm) to increase heat transfer from the barrel walls, and the temperature was increased from 150 °C to 155 °C. These changes resulted in granule growth with the modified elements. The granules produced with the 60° and 90° had good tablet-ability (figure 4) and facilitated lower barrel temperature setpoints as compared to the standard kneading blocks (115 °C vs. 150 °C) for optimized conditions. It is worth noting that the Mannitol formulation did not exhibit any attrition in particle size from the mean. This indicates that it could be a poor representation of drug degradation and further studies will be performed with a more representative compound to analyze the modified kneading block design on drug degradation.

Conclusion: Overall, a reduction in peak shear inherent with utilizing a new design of kneading elements with increased overflight gaps was shown to have promise to improve the twins screw extrusion granulation process. In addition to hardware modifications, several processing factors were identified to improve granule formation and tableting with minimal fines. Further studies will be performed to better understand the result of how key hardware and process parameters affect each other.

References: (1) Tongzhou Liu, Brian Haight, Augie Machado, Charlie Martin, Feng Zhang: Poster presentation on ‘The influence of binder addition methods on continuous twin-screw melt granulation’ at AAPS 2020.
(2) Adwait Pradhan, Brian Haight, Augie Machado, Charlie Martin, Mike Thompson, Feng Zhang: Poster presentation on ‘Effect of Kneading Disk Geometry on Twin-Screw Continuous Melt Granulation’ at AAPS 2022.