Engineering Conferences International ECI Digital Archives Single-use Technologies II: Bridging Polymer Science to Biotechnology Applications Proceedings 5-8-2017 Tie layer technology for multilayer coextrusion of single-use biopharma bags Barry A. Morris DuPont, USA, barry.a.morris@dupont.com Follow this and additional works at: http://dc.engconfintl.org/biopoly_ii Part of the Materials Science and Engineering Commons Recommended Citation Barry A. Morris, "Tie layer technology for multilayer coextrusion of single-use biopharma bags" in "Single-use Technologies II: Bridging Polymer Science to Biotechnology Applications", kta Mahajan (Genentech, Inc., USA) Gary Lye (University College London, UK) Regine Eibl-Schindler (Zurich University of Applied Science, Switzerland) Eds, ECI Symposium Series, (2017). http://dc.engconfintl.org/biopoly_ii/59 This Abstract and Presentation is brought to you for free and open access by the Proceedings at ECI Digital Archives. It has been accepted for inclusion in Single-use Technologies II: Bridging Polymer Science to Biotechnology Applications by an authorized administrator of ECI Digital Archives. For more information, please contact franco@bepress.com.
Tie Layer Technology For Multilayer Coextrusion of Single-use Biopharma Bags Barry Morris Technical Fellow DuPont Performance Polymers Single-use Technologies II: Bridging Polymer Science to Biotechnology Applications Tomar, Portugal May 7-10, 2017
Outline Why tie resins? Basics of polymer adhesion and tie resin technology Factors that affect adhesion and tie resin selection Chemistry of tie and substrate Structure design Process/Processing End use Specific considerations for biopharma applications Summary/Conclusions
Performance Factors for a Single-Use BioPharma Bag Toughness, Flex crack resistance Durability Strong seals Moisture control (ingress and egress) Oxygen and other gas permeation Minimal interaction with the bio ingredients Stability over time (e.g. moisture effect on PA) It is difficult to achieve all of these needs with a single material!
Performance Needs are Met by Multilayer Film Structures Technologies to create multilayer films Adhesion or extrusion lamination: bonding of films in the solid state with an adhesive (solvent, water or chemical based) or polymer melt Coextrusion: bonding of polymer layers in the melt during the film fabrication process (blown film, cast film, etc.) Thermal lamination: bonding of films through application of heat Example structure used for biopharma single-use bags: (LLDPE-tie-EVOH-tie-mPE) coextrusion Coextrusion tie resins are the topic of this presentation
Why a Tie Layer? Acid Copolymer Sodium Ionomer Zinc Ionomer EVA LDPE HDPE Polypropylene Polystyrene Nylon 6 EVOH Polyester Polyester u EVOH Nylon 6 Polystyrene Polypropylene HDPE u LDPE u EVA Good Zinc Ionomer u Fair Sodium Ionomer Poor Acid Copolymer
Polymer Adhesion Mechanisms Wetting/Thermodynamics Diffusion at the interface Chemical interaction at the interface For coextrusion, adhesion is controlled primarily through the latter two mechanisms
Polymer Diffusion Most polymers are not miscible G m RT = A ln N A + B ln A N B + A B + G H B RT Gibbs free energy of mixing: G m < 0 for miscibility Combinatory Entropy. N is large, so this term is nearly zero. Interaction Parameter is always positive Negative when specific interactions are present
Polymer Diffusion Most polymers are not miscible G m RT = A ln N A + B ln A N B + A B + G H B RT Gibbs free energy of mixing: G m < 0 for miscibility Combinatory Entropy. N is large, so this term is nearly zero. Interaction Parameter is always positive Negative when specific interactions are present Polymer miscibility is only achieved when specific chemical interactions are present. Compatibility is improved when interaction parameter is small.
Adhesion Mechanisms Diffusion Limited mostly to polymers within the same family: PE-PE, PP-PP, etc. Little diffusion between nonpolar and polar polymers: PE-PA, PE-EVOH Chemical Interaction Polar polymers often have a reactive site EVOH: hydroxyl groups PA: amine end groups These sites can be used to promote chemical bonding Hydrogen bonding Induced dipole Covalent bonding
Strategy for Bonding in Coextrusion PE Tie EVOH Adhesive is polyethylene or ethylene copolymer based to promote diffusion at PE/Tie interface Adhesive has anhydride or acid groups for chemical interaction at Tie/EVOH interface
Typical Tie Resin Composition Polyolefin matrix or base resin Promotes diffusion at a polyolefin interface Functional groups Promote chemical interaction at interface Other modifiers Toughening component to improve adhesion Additives to improve processability (e.g. antioxidants; fluoroelastomers to prevent melt fracture)
Why Polyolefins as the Matrix Resin? Cost Most structures involve bonding to a polyolefin layer No chemical hook Must rely on diffusion/compatibility Easy to modify to add chemical functionality Co-polymerization Grafting Good mechanical properties for minimizing delamination Combination of toughness and flexibility
Matrix Resin Technology Matrix resins are selected that provide the proper combination of properties: polarity compatibility reactivity bulk physical properties The matrix resin generally determines other performance attributes such as clarity, moisture barrier and temperature resistance.
Peel Strength to EVOH, g/25mm Bonding in Coextrusion: The Effect of Matrix Resin (HDPE-Tie-EVOH) Blown Film 1200 1000 800 600 400 200 0 HDPE LLDPE LDPE Tie-Resin Base Resin Blown Film Line Plasticmachinerysales.com
Tie Resin Functionality FUNCTIONALITY Acid Anhydride Acetate Acrylate BONDS TO: Metal, metallized films, paper, PA, ionomers EVOH, nylon (PA) PVC, PVDC, PET, PS, PP, ionomers Similar substrates as acetate, plus some inks
Peel Strength to PA, g/25mm The Effect of Chemical Functionality (Ionomer - Tie - PA 6) Coex Blown Film 1800 1600 1400 1200 1000 800 600 400 200 0 0 5 10 15 % Acid in Tie Resin Factors include Type of Functionality Amount of Functionality Modifiers
Tie Resin Selection: Structure Considerations What is the structure? To what will the tie resin bond? What types and grades of materials will be used? What is the thickness of each layer?
Peel Strength to PA, g/25mm Effect of Structure: Structural Resin Chemistry ([PA 6 + Amorphous PA] Tie LDPE) Blown Film 2000 1800 1600 1400 1200 1000 800 600 400 200 0 0 20 40 60 80 100 % PA 6 in PA Blend
Peel Strength to EVOH, g/25mm Effect of Structure: Non-Tie Layer Physical Properties (25µ EVOH - 7.5µ Tie - 50µ Sealant) Blown Film 1200 1000 800 600 400 200 Tie 1 Tie 2 Tie 3 Tie 4 0 Ionomer Sealant Type EVA
Peel Strength to OPET, g/25mm The Effect of Structure: Thickness OPET//(Tie - Ionomer) Coextrusion Coating 900 800 700 600 500 400 300 200 100 0 20 25 30 35 40 Tie-Ionomer Thickness, µm
Tie Layer Selection: Processing Considerations What rheology is needed? Tie layer rheology must be compatible with other materials in the structure to avoid a viscosity mismatch What is the process? Processes which involve rapid cooling are more stringent than those with slower cooling At what temperature is the process run? Higher temperature generally improves adhesion Process temperature window of adhesives must be considered
Peel Strength to EVOH, g/25mm Effect of Process: Process Type (PP-Tie-EVOH) Coex Film 2500 2000 1500 1000 500 A-1 A-2 0 Cast Film Line Castfilmextruder.com 9-mil Cast Film Process 3.5-mil Blown Blown Film Line Plasticmachinerysales.com
Tie Layer Selection: End Use Considerations What tie layer physical properties are required? Clarity MVTR Modulus Thermal resistance Puncture resistance/toughness Abuse resistance (folding into cartons, fusing of ports and sensors) Gamma radiation resistance What regulatory compliance is needed?
Tie Layer Selection: End Use Considerations What level of peel strength is required? Is the product exposed to an aggressive environment? Does the tie resin contain additives/residuals that may migrate into the product?
Special Considerations for Single-Use BioPharma Bags Tie resins may contain additives/residuals used in the manufacture of polyolefins, such as Residual monomers (e.g. ethylene, propylene, anhydride) Residual catalysis (especially for LLDPE) Catalysts deactivators Residual acids (from deactivation of catalysts) Acid scavengers (e.g. zinc stearate, calcium stearate, zinc oxide, dihydrotalcite) Oils and other processing aids Reactive impurities (e.g. polyanhydride) Antioxidants (hindered phenols, phosphites) Process aids (e.g. fluoroelastomers to prevent melt fracture of LLDPE) Nucleating and clarifying agents (typically for PP: sodium benzoate, talc, kaolin, dibenzylidene sorbitol)
Special Considerations Tie resins may contain other additives with low MW components Tougheners Tackifiers Plasticizers Degradation byproducts may be created in the film manufacturing process Partially oxidized polymer Oxidative byproducts: aldehydes, acids and ketones Chain scission byproducts
Special Consideration: Tie and Barrier Layer Location Polyolefin contact layers and tie resins may extract components of the bioreaction (scalping) impart low MW components into the reactor (impartation) Barrier layer often provides some protection Position all or part of the barrier layer close to the inside Film Impartation into the bioractor Scalping of ingredients from the bioreactor
Special Consideration: Tie and Barrier Layer Location Caveats: Gas barrier may not be effective small molecule barrier Species may migrate across layers all layers should be considered. Contaminates from outside layer may transfer to inside layer in roll. Moving the barrier layer closer to the inside may affect other properties, such as curl gas permeation (by changing moisture equilibrium) bending stiffness of the film. DuPont has developed models that can help predict these issues. Backside contacts front side of film in roll Picture: dorectomdistry.com
Special Considerations: Handling and Sterilization Flex crack resistance Complex shapes, complicated seals, multiple ports Reactor stuffed into protective box for sterilization Gamma sterilization Compliance with relevant regulations Radiation resistance generally improves with Higher MW, narrower MWD Presence of antioxidants Lower crystallinity: LLDPE more resistant than HDPE Additives may be present that create byproducts. Should test actual package and not base decisions on resin type alone. Thermal stability: reactors see 140 F for several hours during sterilization
Summary Adhesion in coextrusion is complex and is affected by many factors Consider the film structure, the film manufacturing process, and the specific needs when selecting a tie resin It is important to test the peel strength performance under conditions that simulate manufacture and use Work with the supply chain to determine what additives and byproducts may be present that could affect the biopharma reaction
Questions? Barry Morris DuPont Performance Polymers barry.a.morris@dupont.com