(M1530-02-11) Die Modeling for Extruded Implants

Purpose: Processes via twin screw extrusion (TSE) generate some of the most cutting-edge drug delivery systems available today. Significant progress has been made toward improving the continuous extrusion of ocular, hormonal, and multi-layer implant devices. Multi-layer implants are possible using a coextrusion process where two materials are simultaneously extruded through the same die producing a single product with distinct individual layers where die design is critical in determining the final shape, and uniformity of the finished product. Rheology is crucial for designing an extrusion die as it provides critical information viscoelastic properties and flow characteristics under pressure and shear. Computer modeling is a useful tool to improve the dimensional stability and shear stresses experienced by the material for mono and multi-layer structures.

Methods: Two (2) Twin Screw Extruders were used to develop the characteristics required for direct extruded implants. Formulations were developed on TSEs, the rheology work performed (Discovery HR-2 rheometer 8 mm parallel plate at 140 °C), and a candidate die was evaluated and improved. This development included changes to the internal flow paths (spider vs. spiral design) and the bushing and mandrel designs. Dimensional results were confirmed with a Zumbach laser gauge (ODAC X-Y non-contact dual plane laser scanner) with a specified tolerance of ±3% deviation for the diameter. Optimized extrusion process parameters including throughput vs. rpm ratio, gear pump speed, and screw design were evaluated to improve mixing quality, decrease degradation, and improve the consistency of flow and pressures. The core was extruded using a model ZSE-18 TSE (Leistritz, 18 mm diameter screws, 3.2 cc/diameter volume) paired with a Gear Pump (Zenith, Pep-II, 1.5 cc/rev) at 900 grams/hr of Ethyle Vinyl Acetate (EVA, 28 wt.% VA content), and the cap layer with a nano-16 low volume TSE (Leistritz, 16 mm diameter screws, 1 cc/diameter volume) at 100 grams/hr of Ethyle Vinyl Acetate (EVA, 14 wt.% VA content). This gave a total throughput of 1000 grams/hr with 90% in the core and 10% in the cap. Flat temperature profiles of 130 °C were used for both machines resulting in die pressure in the range of 350 - 450 psi. To fully understand the implications of a candidate die design, detailed flow modeling was performed on a multilayer structure by Compuplast.

Results: A crosshead coextrusion die was modeled using EVA 28 as the core layer and EVA 14 as the outer layer as model polymers. Flow geometries, pressure drop, shear stress and shear rate in the die were analyzed for potential impact on residence time and overall part quality. Initial results indicated a layer distribution issue, due to uneven flow caused by inadequate shear rates within the die body. This was then tested and confirmed (figure 1). After adjusting the die design to account for these issues, including changing from a spider to a spiral die design and modifying the bushing and mandrel, the process was again tested and confirmed to have adequate layer distribution (figure 2). In combination with die design, accurate feeding and stable inlet pressures resulted in stable dimensions verified using the Zumbach laser gauge (figure 3). Lower gear pump rpm (within reason, too low caused extreme high pressures) paired with higher throughput and lower extruder rpm resulted in more stable pressure with approximately ±1.5% dimensional fluctuations, within the ±3% target.

Conclusion: By using computer modeling, the internal flow geometries of the coextrusion die were optimized to produce an implant with uniform inner and outer layer distribution and outer diameter dimensional stability. Design variables including die volume, flow convergence angle, pressure drop and shear rate impact on the layer uniformity in the finished product.  Computer modeling saved significant time and cost compared to a trial and error process to develop a quality coextruded part.

References: 1) Zhong, Ziyue “Manufacture, characterization, and drug release of ethylene vinyl acetate-based etonogestrel implant.” Leistritz Twin Screw Workshop, Austin, TX Dec 11, 2024.
2) Perdikoulias, John “Die Design Modeling.” Leistritz Twin Screw Workshop, Branchburg, NJ Dec 4, 2024.

Figure 1: Modeling, representative spider die design, and actual result of poor layer distribution.

Figure 2: Modeling, representative spiral die design, and actual result of adequate layer distribution.

Figure 3: Trended results of factors influencing diameter stability.