PVC is a dominant material used for the storage of IV fluids, dialysis solutions, blood and blood products. This is because of its clarity, strength, ability to withstand temperatures as low as –40ºC and as high as +121ºC, sterilization with steam, ETO and gamma radiation. In addition, PVC can be joined together by high frequency welding which offers the possibility of making containers with complex shapes and with various attachments, thus providing numerous design possibilities. The commercially available PVC is highly branched, has low crystallinity and has structural defects. PVC with high molecular weight (K-Value > 100 with number average molecular weight up to 150,000) have a number of advantages – they have more ordered structure, are more linear, have higher degree of crystallinity and higher mechanical strength. Use of such higher molecular weight PVC results in containers having better strength and superior characteristics and better surface finish. PVC partially cross-linked during polymerization results in PVC resin containing microscopically polymerized particles which are not thermoplastic. When extruded, the sheets and tubes have a matte surface finish (self-frosting characteristics) and find increasing use in fluid transfer applications. PVC itself is compatible with many polymers. Its compatibility with non polar polymerics – such as PE or PP could be enhanced by the use of compatibilizers. Such alloys have enhanced electrical properties, high temperature stability, greater low temperature flexibility, and superior barrier properties.
The most preferred plasticizer for medical grade PVC is DEHP commonly known as DOP even though other plasticizers could be used for specialized applications. DEHP plasticized PVC containers have been used for the collection of blood and blood components for the last 45 years. DEHP has been shown to have very beneficial effects in maintaining the viability and long-term storage of RBCs. Other components in blood such as platelets have a higher metabolic rate and so containers for their storage must have higher permeability to oxygen and carbon dioxide. This is achieved by using other plasticizers such as trimellitates and citrates.
Metallocene PE has purity along with clarity that is required for medical applications and also has low sealing temperatures which make them suitable as alternative to plasticized PVC in medical applications. The material, however, still cannot meet the bonding and sealing requirements of medical products that PVC can. They have no dipole and so cannot be sealed by radio frequency using normal welding equipment.
The performance characteristics of homopolymers such as polyolefins can be enhanced by blending with plastomers. The resultant random copolymers have reduced stiffness and impact resistance while retaining their clarity which makes them suitable for a wide variety of applications.
Blends of polyurethanes with polyesters, PP, EVA and SEBs as mono layers have been found to be suitable for making blood bags and tubing.
Cross linking of polymers leads to improved thermo mechanical properties and chemical resistance. Polymers which could be cross linked are SBS/SEBS, TPO, TPU, Copolyester (COPE), Copolyamide (COPA).
Film laminates in different configurations have been developed for specific medical, food and packaging applications. The films are characterized by clarity, low temperature stability and good barrier properties.
A laminate suitable for IV fluids and form fill seal technology consists of liner LLDPE – oriented nylon – liner LLDPE. Dow Chemicals have developed multi layer laminates suitable for cast and blown film extrusion processes and using polyethylene and polypropylene SARAN resins. These combine the barrier properties of ‘SARAN” with the machinability and printability of polyolefin skins. LLDPE–SARAN–LLDPE laminates are used for containers for premixed drugs. Laminates consisting of LLDPE with PP impact copolymer with outer skins of random copolymers have been developed for packaging purposes by Basell.
HF weldable polyolefin films have been developed for medical infusion bags and blood bags based on co extrusion of polyolefin skins such as PP or LLDPE with reactive core layers such as PET, nylon, TPUS and blends or co extrusions with SEBS/SBS.
A steam sterilized polyester modified PP film suitable for intravenous solution containers is marketed by Cryovac.
EVA is RF/heat weldable plastic which can be used for blood bags and tubes where the absence of plasticizers is an advantage. However, it cannot be steam sterilized. Tackiness and abrasion of sheet surfaces are problems. Various ways have been devised to overcome these problems such as the empty bags could be rendered steam sterilizable by cross linking by the use of high energy radiation, the EVA film could be coextruded with HDPE outer skins to improve WVTR and prevent surface abrasion.
TPU films have excellent strength, toughness and water vapour permeability and are readily sealable by RF. It has lower density than PVC which gives it more film area per kilogram. However, they are more expensive than PVC.
PVC Nylon blends have been used for enhanced physical strength and high temperature properties. PVC-urethane blends have higher abrasion resistance; have low extractable and higher water vapour transmissions. PVC-poly olefins give comparatively softer films with high oxygen barrier properties.
Various novel approaches are under study to give improved characteristics to PVC:
* Moisture Curing of PVC
PVC or vinyl chloride is copolymerized or grafted with certain specific silane monomers. Devices or tubes fabricated using such PVC could be cross linked by exposing them to high humidity for short periods. Efforts are under way to develop PVC composed of blocks of syndiotactic, atactic and so tactic resins designed to give polymers of varying levels of Crystallinity and Glass transition temperatures.
* Copolymerization of Vinyls with olefins
Highly ordered copolymers or block copolymers have been made by copolymerization of vinyl chloride with comonomers such as olefins. The product combines the properties of polyolefins and vinyls.
Plasticizers are not covalently bonded with PVC and so could migrate out of the containers particularly in the presence of solubilising lipids, lipoproteins and albumin. In 1970, a study showed that DEHP from blood bags leached into stored human blood. But today it has been proved that there were shortcomings in studies made using rats and mice as models since there are significant differences in the metabolism of DEHP between rodents and humans. In 1999, a blue ribbon panel comprising of eminent toxicologists, clinicians and other scientists concluded that DEHP is not harmful to even highly exposed people, those who undergo certain medical procedures such as regular haemodialysis or extra corporeal membrane oxygenation. The panel concluded that DEHP imparts a variety of important physical characteristics that are critical to the function of medical devices and eliminating DEHP in these products could cause harm. Concerns regarding PVC continue to be raised regarding the toxic effluents produced during the manufacture of PVC and the generation of hydrochloric acid and other harmful chemicals during the incineration of PVC wastes. Other concerns relate to the environmental hazards of plasticizers used, particularly DEHP which could migrate from refuse dumps into the soil and then to water bodies. In medical products it is the leaching of DEHP into intravenous solutions or blood and blood products when stored in PVC container that is of concern. Hence concerted efforts are under way to overcome these problems by developing alternatives to PVC, making modification to PVC and by the development and use of newer plasticizer to PVC.
Phthalates other than DEHP such as DIDP and DINP which have lower extraction compared to DEHP have been used for plasticizing PVC for making medical devices.
Di-(2-Propyl Heptyl Phthalate is an innovative product of BASF, marketed as Palatinol 10-P. This plasticizer has the same efficiency as DIDP and has the advantage of less odour.
Di, (2-ethyl hexyl) terephthalate has been developed as a plasticizer for medical grade PVC in a joint project of Eastern Chemicals Company and Solvay Draka Inc. The biological activity of DEHT is different and safer than that of DEHP.
Di, (2-ethyl hexyl) adipate has low toxicity as compared to DEHP and is readily absorbed and metabolized to harmless products. It has higher solubility in water and so is more prone to migration into solutions stored within containers made of PVC containing this plasticizer. Poly adipates have much less leaching characteristics.
DEHA however has not found much favour for making containers for the storage of blood and blood products.
The plasticizer tri, (2-ethyl hexyl) trimellitate (TEHTM) has extremely low leachability into water or blood plasma. Blood Bags made using PVC with this plasticizer have been found to be very good for the storage of platelet rich plasma for more than five days and has been used by reputed blood bag manufacturers for this purpose. DEHP free PVC using TEHTM plasticizer has been developed by Rohan Ltd.
Blood Bags made using this plasticizer is not however suitable for the storage of blood or red cell concentrates for long periods which is directly due to the non-leaching nature of the plasticizer.
The most satisfactory plasticizer is n-butyryl, tri n-hexyl citrate (BTHC) for medical applications. Blood bags made using this plasticizer have been found to be effective for the storage of blood, red cell concentrates and platelet rich plasma.
BTHC has very low toxicity and is metabolized into harmless compounds such as citric acid, butyric acid and hexanol.
Another advantage is its low glass transition temperature of –27ºC as compared to –4ºC for DEHP plasticized PVC.
Hexamol is an innovative plasticizer introduced recently by BASF for sensitive applications under the name DINCH. It has a proven excellent toxicological profile, no carcinogenicity, and low migrating characteristics It has a wide range of regulatory approvals and is approved for toys and food contact applications.
Terumo Penpol Ltd has found that PVC containers made using this plasticizer are suitable for the storage of platelets for up to six days. This plasticizer is also suitable for making containers with low leaching characteristics for the storage of solutions for dialysis and for parenteral applications.
Plasticized PVC holds a dominant position for the fabrication of medical devices and for the storage of blood and blood products. Concerns about the leaching of the most favoured plasticizer DEHP, particularly its possible adverse effects caused serious apprehensions and led to efforts to find replacement to PVC. Even though a series of subsequent authoritative reassessments dispelled most of the apprehensions, its possible ill effects on neonates and other susceptible groups continues to cause worries.
PVC itself is holding on to certain critical areas such as containers for blood and blood products, and specialized medical tubing. Higher molecular weight PVC is the preferred type for medical film and tubing. A novel approach is the production of block copolymers of vinyl chloride and olefins, which combine the characteristics of PVC and olefins. New alloys of PVC with other polymers are replacing high priced materials such as thermoplastic elastomers, TPOs, TPUs and silicones.
The developments relating to polyolefins and PVC have great potential for applications in future. The processes and technologies however, need a lot more development to enable the manufacture of specialized products at reasonable costs.
PVC is the most economical material for medical application and unless the other alternatives match in price PVC will continue to dominate as the market leader in medical applications.
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