Commodity Thermoplastics

6 Commodity Thermoplastics: Polyvinyl Chloride, Polyolefins, and Polystyrene 6.1 Introduction Commodity thermoplastics comprise polyvinyl chloride (PVC), polyolefins (polyethylene, polypropylene, and their blends), and polystyrene (PS). Over 75% of all plastics used in medical device applications use commodity thermoplastics. Their low cost, excellent performance, and easy processability make them attractive candidates for medical device applications like labware, tubing, medical films, collection bags, catheters, IV components, surgical instruments, sutures, vials and ampoules, gloves, syringes, packaging, and implants. This chapter will describe the structure, manufacture, properties, and applications of these materials for medical devices. Although not considered a commodity resin, cyclo olefin copolymers (COCs) also will be discussed in this chapter.

6.2 Polyvinyl Chloride (PVC) Polyvinyl chloride is the most widely used resin in medical devices. Approximately 25% of all plastic medical products are made of PVC, according to most market estimates. The main reason is the resin’s low cost, ease of processing, and ability to tailor its properties to a wide range of applications. Among the numerous medical applications of PVC are blood bags and tubing, gloves, dialysis equipment, mouthpieces and masks, oxygen delivery equipment, labware, catheters, injection molded parts, and device packaging. PVC covers a wide range of properties shared by substances spanning from rubbers to engineering thermoplastics, as shown in Figure 6.1 [1]. PVC formulations can range from soft, flexible materials to hard, rigid plastics. Major factors for the use and popularity of PVC in medical device applications are the following:

• PVC has been used successfully for over 50 years in various medical devices with no known adverse or toxic effects. Experience

based on all available knowledge from international environmental and healthcare authorities shows that PVC is safe. It is the best material existing today, which optimizes all performance and safety requirements at the lowest cost.

• Plasticized PVC has good clarity so that tubes and other products retain their transparency to allow for continual monitoring of fluid flow. In addition, PVC has high gloss and appealing aesthetic value.

• PVC can be manufactured in a range of flexibilities, and its unsurpassed resistance to kinking in tubing reduces the risk of fluid flow being interrupted. In addition, PVC can be used in a wide range of temperatures, and it retains its flexibility, strength, and durability at low temperatures.

• PVC formulations exhibit excellent strength and toughness. For example, vinyl gloves possess very good resistance to tearing, which protects both doctors and patients and helps prevent the spread of infection, germs, and disease.

• PVC exhibits very good chemical resistance and stability and is also biocompatible for applications in blood bags and drug delivery. These properties can be tailored by appropriate formulations and surface modifications. PVC is compatible with virtually all pharmaceutical products in healthcare facilities today. It also has excellent water and chemical resistance, helping to keep solutions sterile.

• Plasticized PVC maintains its product integrity under various sterilization environments like steam, radiation, and ethylene oxide (EtO). PVC can easily be extruded to make IV tubing or films, thermoformed to make “blister” packaging, or blow molded to make hollow rigid containers. It can be injection molded to form various components and parts. This versatility is a major reason why PVC is the material of choice for medical products and packaging.

Plastics in Medical Devices. DOI: http://dx.doi.org/10.1016/B978-1-4557-3201-2.00006-9 © 2014 Elsevier Inc. All rights reserved.

73

74

PLASTICS

IN

MEDICAL DEVICES

Polyvinyl chloride (PVC)

Thermoset Elastomers

Thermoplastics

Thermoplastic Elastomers

10

20

30

40

50

60

70

80

90 95

Shore A Durometer 30

40

50

60

70

80

Shore D Durometer

50

70

90

110

120

130

140

150

90 95

Rockwell R Hardness

Figure 6.1 Broad range of PVC properties.

• PVC can be easily welded to various other plastics via a wide range of methods. Collection bags and oxygen tents can be constructed using these welding techniques.

• PVC plays a big role in containing rising healthcare costs. Its relatively lower cost and high performance value maintains its position as the number one plastic used in medical devices. PVC is a material that meets the performance, safety, and cost criteria for a wide variety of medical applications, especially for single-use disposable devices. It is also easily processable to produce a wide variety of products.

6.2.1 PVC Manufacture Polyvinyl chloride is manufactured from vinyl chloride, which is a gas at room temperature. Vinyl chloride is polymerized via free radical polymerization by suspension, bulk, emulsion, and solution methods. The basic free radical polymerization process is shown in Figure 6.2.

CH2 CH2

CHCl

Catalyst

CH

Cl Vinyl chloride

n

Polyvinyl chloride (PVC)

Figure 6.2 Synthesis of Polyvinyl chloride.

prevent coalescing of the droplets. Vinyl-soluble free radical initiators like lauryl peroxide or azobisisobutyronitrile are added, and polymerization occurs around 50 C. The resulting polymer has a high molecular weight and is crystal clear. The polymer is centrifuged from the reaction mixture, washed, and dried. PVC resins made by suspension polymerization for rigid applications are generally less costly to produce than those for flexible applications because they can be polymerized at high conversion rates and are easily stripped of residual monomers. PVC for flexible applications must be porous so that they can absorb plasticizers. Applications include injection molding and extrusion (film, tubes).

6.2.1.1 Suspension Polymerization Vinyl chloride is dispersed into very fine droplets by vigorous stirring in water. Protective colloids (0.05 0.1% of the weight of vinyl chloride), like polyvinyl alcohol or substituted celluloses, are added to

6.2.1.2 Emulsion Polymerization Vinyl chloride is emulsified in water by adding surfactants and emulsifiers with vigorous stirring. Watersoluble initiators like persulfates are used

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

for polymerization. Purification and drying of the resulting polymer results in a material that is more expensive than a resin produced by suspension polymerization. However, the polymer in the emulsified state (also known as a plastisol) also can be used. Examination and surgical gloves use plasticols for their manufacture.

6.2.1.3 Bulk Polymerization Bulk polymerization is a two-stage process. In the first stage, pure vinyl chloride monomer is polymerized up to 10% conversion using monomer-soluble free radical initiators. In the second stage, more monomer is added and the mixture is polymerized with up to 80 85% yield. The excess monomer is stripped off using a vacuum and dried. PVC obtained from this process is pure, crystal clear, with a narrow particle size distribution. Applications include blow molded bottles.

6.2.1.4 Solution Polymerization In solution polymerization, vinyl chloride is dissolved in organic solvents and polymerized with an organic soluble initiator. The polymer precipitates from the solution is filtered, washed, and dried. This process is used to make specialty copolymers with vinyl acetate.

6.2.2 PVC Additives Virgin PVC is not a very useful resin. Various additives are generally compounded into PVC to give the material a diverse set of properties ranging from rigid to flexible [2].

6.2.2.1 Heat Stabilizers Heat stabilizers are typically used in medicalgrade PVC, not only to protect it against the high

75

temperatures the resin might see during processing, but also the high heat it may encounter in storage or autoclaving [3]. Barium-zinc additives are very effective heat stabilizers for PVC but are restricted for medical applications in some countries. Alternatives like calcium-zinc formulations are often used to stabilize medical-grade PVC against heat. Heat stabilizers trap the hydrogen chloride that is generated when PVC decomposes at high temperatures and prevent discoloration and degradation, as shown in Figure 6.3 [4]. Rigid PVC typically contains between 10% and 15% by weight of additives like heavy metal salts of lead, tin, barium and zinc, or organotin compounds.

6.2.2.2 Plasticizers Many types of plasticizers are used to produce flexible PVC. These plasticizers are incorporated in amounts ranging from 40% to 65% and are typically long-chain alcohol esters of phthalic acid and citric acid. The most commonly used plasticizer is di-(2-ethyl hexyl phthalate) (DEHP), whose structure is shown in Figure 6.4. Increasing the amount of DEHP will improve the flexibility and reduce the hardness of the material [5]. Figure 6.5 shows the effect of DEHP level on the Durometer Shore A hardness of the resulting plasticized PVC. Some of the other plasticizers used in medical applications are the following:

• • • • • • •

Dioctyl phthalate, Di-n-decyl phthalate, Acetyl n-tributyl citrate, Acetyl n-trihexyl citrate, Butyryl-n-trihexyl citrate, Epoxidized soybean oil (ESBO), and Epoxidized linseed oil (ELO).

Cl

OCOR + ZnCl2

Zn(O2C-R)2 +

ZnCl2

+ Ca(O2C-R)2

Ca(O2C-R)2

+

HCl

Zn(O2C-R)2 + CaCl2 HO2C-R +

CaCl2

Figure 6.3 PVC stabilization in the presence of zinc/calcium carboxylate additives.

76

PLASTICS

IN

MEDICAL DEVICES

Table 6.1 Typical Formulation of Plasticized PVC O

O O

O

Figure 6.4 Structure of PVC plasticizer di-(2ethylhexyl) phthalate DEHP.

Plasticizers reduce the hardness and improve the flexibility of PVC. DEHP exhibits good compatibility, light stability, low volatility, high water resistance, good electrical properties, low temperature flexibility, and an excellent overall costto-performance ratio. DEHP is also resistant to sterilization methods like EtO, autoclave, steam, and radiation. In addition, the plasticizer provides high transparency to PVC, which is especially important for medical device applications. Tubing made from plasticized PVC is transparent, flexible, and nonkinking. This enables the delivery of the right dose of critical fluids to the patient and can be monitored visually. A typical formulation for plasticized PVC is listed in Table 6.1. In Europe, DEHP is the plasticizer recommended in the European Pharmacopoeia for medical devices, and PVC containers are the only type listed for use with blood, blood components, and

Component

Parts per hundred (pph or phr)

PVC

100

Plasticizer

20 45

Stabilizer

2 3

Epoxy

2 3

Impact modifier

4 6

Processing aid

1 2

External lubricant

0.2 0.3

Pigment

As per color requirement

aqueous solutions for intravenous infusion [6]. An advantage of DEHP-plasticized PVC in the storage of red blood cells is that DEHP actually binds to red blood cells, preserving them and extending their shelf life. Other materials for this application can be used only after they are approved for use by the respective regulatory bodies. Recently, phthalates have come under intense pressure due to fears of carcinogenicity and estrogen interference. Several reports and reviews detail the various studies and conclusions derived from these studies. It has been reported that because the plasticizers used with PVC are not chemically bound to the polymer, they can leach out when in contact with certain media [7 13]. Some plasticizers (particularly DEHP, which is the most widely used) have been associated with a range of adverse effects in laboratory animals. However, the ability of DEHP to produce such

Effect of DEHP Loading on Durometer Shore A of PVC 105

Shore A Hardness

100 95 90 85 80 75 70 65 0

10

20

30

40

50

60

70

DEHP Loading (phr)

Figure 6.5 Effect of DEHP loading on the Durometer Shore A hardness of PVC.

80

90

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

effects in humans is controversial. The US Food and Drug Administration (FDA), in a publication entitled “Safety Assessment of DEHP Released from PVC Medical Devices,” [14] identifies a list of products known to release DEHP. The list includes the following:

• • • • • • • • • • • • • • • • •

IV storage bags, Ventilator tubing, IV infusion sets, Endotracheal tubes, IV infusion catheters, Nasogastric tubes, Blood storage bags, Enteral and parenteral nutrition storage bags, Blood administration sets, Urinary catheters, PVC exam gloves, Suction catheters, Chest tubes, Nasal cannula tubing, Hemodialysis tubing, Syringes, Extracorporeal membrane (ECMO) tubing, and

oxygenation

• Cardiopulmonary bypass (CPB) tubing. The basic conclusion from these studies is that no quantitative estimates of risk or safety levels to humans at various stages of life or health can be established with confidence. This is because most studies have been carried out on laboratory animals, and the extrapolation to humans is currently inadequate. Consumers and end users are advised to proceed with treatments using PVC devices and have the choice to switch to non-DEHP-containing devices if available. Materials exist that do not contain DEHP or other similar plasticizers, which are currently being used in medical devices. These materials have the potential to be safer alternatives to DEHP-containing medical devices. A thorough review of the world position concerning PVC/DEHP was reported by the Health and Consumer Protection Directorate-General of The European Commission, through the Scientific Committee on Medicinal Products and Medical

77

Devices, which issued a paper on September 26, 2002, entitled “Opinion on Medical Devices Containing DEHP Plasticized PVC; Neonates and Other Groups Possibly at Risk from DEHP Toxicity”[15]. This paper concluded: “On the basis of the evidence presented in this report, no Tolerable Intake Value for DEHP in medical devices can be recommended.” Significantly, however, the discussion also states: “The contribution of DEHP-PVC to the delivery of health care should be taken into account in the consideration of the potential risks of adverse effects of DEHP in these patients.” The FDA position has been detailed in a paper entitled “Medical Devices Made With Polyvinylchloride (PVC) Using the Plasticizer di-(2-ethylhexyl)phthalate (DEHP); Draft Guidance for Industry and FDA” dated September 6, 2002 [16]. This paper stated that “not all devices made with PVC contain DEHP. Further, FDA recognizes that many devices with PVC containing DEHP are not used in ways that result in significant human exposure to the chemical. Therefore, FDA is focusing attention on the small subset of medical devices where PVC containing DEHP may come in contact with the tissue of a sensitive patient population in a manner and for a period of time that may raise concerns about the aggregate exposure to DEHP. We believe that many devices used in Neonatal Intensive Care Units (NICUs) meet these criteria and should be a primary focus.” The Advanced Medical Technology Association (ADVAMED) includes in its publication “Frequently Asked Questions Regarding PVC and DEHP in Medical Devices” [17]: “For the majority of its applications, medical device manufacturers believe that PVC remains the most appropriate material available because of its unique properties and history of safe use. Any new alternative would lack the long history of tested, proven research that supports the safe and effective use of PVC in medical devices.” The publication also cites the Food and Drug Administration’s position, which states: “Since there is consumer concern, we will look at it again. But we would need to see a substantial amount of testing to make sure that we weren’t moving from a product with good characteristics to one that we don’t know very much about [14]”. Eucomed, the European medical technology industry cooperative body, has published a position paper [18] that concludes: “. . .the many benefits of the continued use of plasticized PVC in medical products totally offset any perceived risks.”

78

PLASTICS

These and other publications on this subject are perhaps best summarized by the European Commission opinion paper [15] that states: “These reviews generally conclude that there should be no concerns for the vast majority of adults in relation to toxicity following DEHP exposure. For children, the situation is different. On the basis of in vitro and in vivo toxicity studies, there are concerns for testicular toxicity, depressed fertility, and reproductive developmental toxicity following oral exposure to PVC containing DEHP in children. In view of these concerns, the use of DEHP in soft toys has recently been forbidden in some areas (European Commission, 1999). However, there are no general concerns for either adults or children in relation to acute toxicity, irritation, sensitization, mutagenicity, or carcinogenicity.”

IN

MEDICAL DEVICES

K-value between 50 and 80. The higher the K-value, the better are the mechanical and electrical properties of the material, and, the higher are its processing temperatures. Table 6.3 gives the K-values of various PVC (plasticized and unplasticized) grades, along with their typical applications, and Table 6.4 compares the various types of PVC materials. PVC can be further chlorinated to produce a higher-heat resistant, flame-retardant material with good weather ability. Three main types of medical products that contain phthalates are the following:

• Containers: Examples include flexible bags for intravenous or nutritional fluids, solutions, drugs, and anticoagulants. They are also used to collect and store blood and plasma (IV blood bags) and to collect urine.

• Flexible tubing: Examples include blood cir-

6.2.3 PVC Properties Unplasticized PVC is more rigid, harder, and stiffer than plasticized PVC, as can be seen from the flexural modulus, and hardness properties. The properties of plasticized and unplasticized PVC are compared in Table 6.2. PVC polymers are identified by their K-values or viscosity numbers. These numbers relate to the molecular weight of the polymers, which in turn determine the properties and performance characteristics for specific applications. PVC resins used for thermoplastic applications typically have a

cuit tubes, infusers, catheters, and endotracheal tubes.

• Protective devices: Examples include gloves and oxygen tents.

6.2.4 PVC Chemical Resistance Unplasticized PVC has a little better chemical resistance than plasticized PVC. PVC is not resistant to organic solvents like chlorinated hydrocarbons, ketones, and cyclic ethers (Table 6.5). PVC is not very compatible with pure ethylene oxide, but can

Table 6.2 Properties of Unplasticized (PVC-U) and Plasticized (PVC-P) PVC Property

Unit

PVC-U

PVC-P

Density

g/cc

1.38 1.4

1.20 1.30

Melting point



C

170 180

170 180

Glass transition temperature



C

80

240 to 20

HDT at 1.8 MPa or 264 psi



C

65 75

20

Tensile strength

MPa

45 55

10 20

Elongation @ break

%

20 100

100 500

Flexural modulus

GPa

2 5

0.01 0.03

Impact strength (notched)

J/m

20 100

90 110

Hardness durometer A

Shore A

—

40 80

Hardness Rockwell

Rockwell R

100 115

—

 40% DEHP. PVC-U Unplasticized PVC. PVC-P Plasticized PVC.

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

79

Table 6.3 K Values of PVC-U (Unplasticized) and PVC-P (Plasticized) PVC Resins Process

PVC-U Emulsion

PVC-P Suspension

Mass/ Bulk

K Values

Emulsion

Suspension

Mass/ Bulk

K Values

Calendering

• Heat treated

75 80

—

—

—

—

—

—

—

—

60 80

60 70

—

• Tubes

70

76 78

67 68

—

—

—

• Sheet and flat film

60 65

60

60

—

—

—

• Blown film

60

57 60

60

—

—

—

• General

—

—

—

65 70

65 70

65 70

Blow molding

—

57 60

58 60

—

65 80

60 65

Injection molding

—

55 60

56 60

—

65 70

55 60

films

• Floor coverings Extrusion (PVC-U)

Extrusion (PVC-P)



DIN 52726-0.25 PVC in 60 ml cyclohexanone

Table 6.4 Comparison of Various Types of PVC Resins Polymer

Advantages

Disadvantages

Rigid PVC

Excellent corrosion resistance

Susceptible to staining

High dielectric properties Good toughness and abrasion resistance Self-extinguishing Good weatherability Flexible PVC

Highly flexible

Stiffens at low temperatures

Good chemical and weather resistance

Susceptible to staining

Inherent self-extinguishing characteristics

Some plasticizers migrate to surface

High dielectric properties Low cost Chlorinated PVC

Excellent corrosion resistance 

Heat resistance .50 F higher than rigid PVC Good toughness and abrasion resistance Self-extinguishing Good weatherability

Difficult to process

80

PLASTICS

be used in ethylene oxide sterilization when exposed to low concentrations of the chemical. The chemical resistance of plasticized PVC is very much dependent upon the type and amount of plasticizer used. In some cases, certain plasticizers can even increase the chemical resistance of PVC. PVC is resistant to stress cracking. Chemical resistance of PVC also can be predicted using solubility parameters [19].

IN

MEDICAL DEVICES

2. A propagation step, during which hydrogen chloride (HCl) is produced; and 3. A termination step, in which the active centers are deactivated. Radicals are formed from CaCl or CaH bond scission reactions [25]. A CaC bond scission also can occur. There is a high probability that the two macroradicals will recombine with each other due to the restricted mobility of the polymer chains in the solid state. Among the three radiation-induced polymeric radicals, “A” and “B” would continue the reaction in which HCl is formed and acts as a catalyst (Figure 6.6). Chain scission can follow, causing degradation, or the radicals can react with oxygen to form oxidized products, leading to discoloration. PVC when formulated with light stabilizers, UV absorbers, and HCl-scavenging stabilizers will render the resin radiation resistant and stable [26 29]. Free radical scavengers and antioxidant stabilizers are used to prevent this degradation by reacting with the free radicals formed when the polymers are exposed to high-energy radiation, rendering the radicals inactive (Figure 6.7). In the presence of a free radical stabilizer, the tensile strength of PVC is retained at high radiation doses (Figure 6.8) [27,28].

6.2.5 PVC Sterilization Rigid, unplasticized PVC is unsuitable for use in steam and autoclave sterilizations because the material and parts will warp and distort in those environments at temperatures of 121 C. Plasticized, flexible PVC can be sterilized using steam or autoclave (Table 6.6). Ethylene oxide sterilization can be used for both rigid and plasticized PVC. When choosing ethylene oxide gas sterilization, a 7- to 14-day quarantine period is necessary to ensure that there is no EtO residue. Low-temperature steam sterilization (conducted at 60 80 C) can be used for both rigid and flexible PVC. PVC will degrade by chain scission when exposed to high-energy radiation [20 23]. The degradation of PVC occurs in a three-step process [24]: 1. An initial step, in which active centers are formed;

Betadine

Lipids

Soaps/ Detergents

Disinfectants

Hydrogen Peroxide

Bleaches

Saline Water

Silicones

Oils/Greases

Ethylene Oxide

IPA

Acetone

MeCL2

MEK

THF

Dilute Basses

Polymer

Dilute Acids

Table 6.5 Chemical Resistance of PVC

PVC PVC plasticized

Good Good Poor Poor Poor Poor Poor Poor Fair Good Good Good Good Good Good Fair Poor

PVC unplasticized

Fair Good Poor Poor Poor Poor Good Fair Good Good Good Good Good Good Good Good Poor

Table 6.6 Sterilization Capability of PVC Polymer

Steam

Dry Heat

Ethylene Oxide

Gamma Radiation

E-Beam

Fair

Fair

Good

Good

Good

Poor

Poor

Good

Fair

Fair

PVC PVC plasticizeda,b PVC unplasticized a

a,b

Radiation stable grades should be considered for gamma and e-beam radiation sterilization. corrective tint to compensate for discoloration.

b

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

CH

CH2

+ Cl

tio

n

CH2

81

γ− r

ad

ia

A

CH

γ−radiation

iat ad γ−r

Cl

CH

CH

CH

Cl

B

Cl

CH2

C

CH2

ion

CH2

CH

CH

CH

+ H

D

+ H

CH

+ HCl

Cl

Oxidation and degradation products

Cl

C Figure 6.6 PVC degradation mechanism.

CH2

γ−radiation

CH

CH2

CH

CH2

O

+ Cl

Cl

Cl

R

CH

R

OH +

+

CH2

Cl

R

CH

CH2

O

+

HCl

CH

CH2

Cl

R = Stabilizer

CH

CH2

OR

CH Cl

Figure 6.7 Mechanism of stabilizing agent for PVC.

Effect of Stabilizer on PVC Degradation with Gamma Radiation 14

Tensile strength (Kgf/mm2)

DEHP

12

DEHP + 0.5% Tinuvin P DEHP + 1.0% Tinuvin P

10

DEHP + 1.0% Tinuvin P

8 6 4 2 0 0

10

20

30

40

50

60

70

Radiation Dose (kGy)

Figure 6.8 Effect of a stabilizer on the tensile strength of plasticized PVC when exposed to gamma radiation.

82

PLASTICS

The plasticizer DEHP causes degradation of PVC during e-beam radiation. Mixing DEHP with epoxidized soybean oil significantly reduces the degradation [30]. PVC will discolor when exposed to high-energy radiation. Proprietary tinting agents that correct the color of the part after exposure to radiation help offset the color change. Figure 6.9 shows the difference in color before and after exposure to gamma radiation between resins that have been color corrected and one that has not been color corrected. The tinted PVC shows no major change in color when exposed to gamma radiation, whereas the PVC resins that were not color corrected show a significant color shift or color change when exposed to gamma radiation [31]. Depending upon the formulation, the color can revert to close to the original color after one to four weeks of storage.

Unexposed control

25 kGy

40 kGy

PVC-1

PVC-2

IN

MEDICAL DEVICES

6.2.6 PVC Biocompatibility PVC is highly biocompatible and hemocompatible. For this reason, it is used for blood bags, drug delivery, catheter tubing, and other applications that come in contact with bodily fluids and tissues [32,33]. Leachable and extractable materials from PVC are mostly derived from the plasticizers used in the formulation. Studies have shown that a significant amount of DEHP leached out of DEHP-containing flexible PVC tubing during hemodialysis [34]. Several other studies show that the amount of DEHP extracted depends upon the reagents making up the solution that is in contact with the PVC bag or tubing [35 37]. When PVC is coated with heparin, its hemocompatibility is significantly increased [38]. DEHP-containing PVC was found to have no cytotoxic effects when analyzed by the ISO 10993-5 standard, as shown in Figure 6.10 [39]. Extracts from plasticized PVC showed no reduction in metabolic activity of cells when compared to a negative control. The positive control had reductions of 26% and 19% for the L929 and HaCaT cells, respectively. Hemocompatibility of DEHP-containing PVC was studied and showed no detrimental effects in fibrinogen adsorption [32].

PVC-3

6.2.7 PVC Joining and Welding

Figure 6.9 Effect of gamma radiation on the color of PVC, with and without tinting agents (PVC-1— color tint, PVC-2 and 3—no color correction).

PVC can be welded by heated tool welding and vibration welding, where strong bond strengths are obtained. Ultrasonic welding efficiency depends upon

Cytotoxicity of DEHP-PVC

120 Negative Control

PVC

% Cell Reduction

100 80 60 40 20 0 L929

HaCaT Cell Type

Figure 6.10 Cytotoxicity of DEHP-containing PVC.

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

the formulation of the PVC part. Mixtures of chlorinated solvents (like methylene chloride) with ketones (acetone) and cyclic ethers (tetrahydrofuran) work well in bonding PVC to itself or to other plastics. Epoxies, urethanes, and cyanocrylate are excellent adhesives in bonding PVC to other plastics.

6.2.8 PVC Blends PVC can be blended with various polymers to tailor and enhance its properties [40]. The main thrust has been to use these blends as alternatives to phthalate-containing plasticized PVC. One of the reasons is to use a nonleaching material that, when blended with PVC, provides the toughness, flexibility, and processability of phthalate-containing PVC at a reasonable cost. PVC is a polar polymer. Nonpolar polymers like polyolefins and polystyrene are not miscible with PVC and do not produce viable materials. Compatibilizing agents need to be used to improve the miscibility between the two types of polymers. More polar polymers like polymethylmethacrylate (PMMA), nitrile butadiene rubber (NBR), polycaprolactone (PCL), polyethylene vinyl acetate (EVA), poly(ethylene-vinylacetate-carbon monoxide) terpolymer (EVA-CO), and polyethylene oxide have been used more successfully in practical applications. A PVC/ABS blend improves the impact strength of PVC without sacrificing its mechanical properties like tensile strength. PVC/PMMA blends possess a good balance of toughness, impact resistance, and durability over a wide range of temperatures. PVC/EVA blends have flexibility and toughness and maintain the clarity of PVC. Like PVC, EVA can come in a wide range of hardness all the way from thermoplastic to elastomeric. Increasing the EVA content improves the clarity, low temperature flexibility, and impact strength of the polymer. Blends of PVC with an EVA-CO terpolymer have a lower tensile strength and flexural modulus than a PVC EVA blend. Increasing the CO content in the terpolymer results in improved miscibility of the PVC blends, which have very similar properties to phthalate-containing plasticized PVC [41]. PVC/EVA, and especially PVC/EVA-CO blends, have been considered as alternatives to phthalate-containing plasticized PVC. Blending PVC with styrene acrylonitrile (SAN) or acrylonitrile butadiene styrene (ABS) produces higher heat materials, which are used in housings for medical equipment.

83

Table 6.7 lists a few PVC blends, their properties, and typical applications.

6.2.9 PVC Medical Device Applications PVC is used in various medical devices and components like the following:

• • • • • • • • • • • • • • • • •

Containers for IV and dialysis fluids,

• • • •

Infusion drip chambers,

Blood bags, Hemodialysis sets, IV sets, Catheters, Dialysis bags, Plasma collection bags, Infusion sets for blood and IV fluids, Examination and surgical gloves, Oxygenators, Endotracheal tubing, Wound and chest drainage tubes, Colostomy bags, Rigid extruded luers and containers, Injection molded components, Surgical drapes, Tubing (cardiovascular, endotracheal, drug delivery, blood, etc.), Blister packaging, Suction pipes, Hospital floors and walls (because vinyl can be joined without seams, reducing the risk of cross-infection),

• Blood bags—blood can be stored in PVC bags for longer periods than would be possible in glass containers; and PVC is the only material approved for use in flexible blood collection containers by the European Pharmacopoeia, • Pharmaceutical products—clear, rigid PVC foil protects them from deterioration and allows easy visual control of dosage, • Blister packs for tablets,

84

PLASTICS

IN

MEDICAL DEVICES

Table 6.7 Properties and Applications of PVC Blends Blend

Properties

Applications

PVC/NBR

Permanent plasticization; excellent flow and physical properties; longterm stability; resistance to fuels, chemicals, and oil; good electrical properties; colorability

Oxygen masks, IV tubes, regulators, gloves

PVC/PMMA

Toughness, impact resistance, durability, processability

Medical equipment housings, MRI fixtures, and receiving coils

PVC/SAN PVC/ABS PVC/SMA

High heat resistance, good weatherability, good processability

Medical equipment parts, connectors

PVC/PCL

Clarity, flexibility, toughness, impact- and kink-resistant

Bags, pouches, tubing, drug delivery

PVC/EVA PVC/EVA-CO

Clarity, flexibility, permanent plasticization

Bags, pouches, tubing, drug delivery

Table 6.8 Typical Applications of PVC Medical Extrusion Compounds

Table 6.9 Typical Applications of PVC Medical Molding Compounds

Shore A Hardness 15 s @ 23 C

Typical Applications

Shore A Hardness 15 s @ 23 C

Typical Applications

30/40/50/60

Soft tubing

15/35/45

Soft molding applications

65

Heart/lung bypass tubing

45/55/65

Face masks

70

Peristaltic pumping tubing

70

Catheter funnels, enema nozzles

50/60/70

Medium soft tubing

75

75

Blood tubing

Blood transfusion and dialysis components

80

Endotracheal tubing, catheters, blood bags

80

Blood transfusion set components

80/85

Medium stiff tubing

90

Drip chamber components

97

Drip chamber components

95

99

Post-formable stiff catheter tubing

Drip chamber components, end caps, luer fittings

• Transfusion and intravenous tubing, and • Surgical gloves. Other applications of PVC within a hospital include water and drainage pipes, fire-resistant cabling in electrical and telecommunications, flooring in operating theaters, and hygienic mattresses. Tables 6.8 and 6.9 summarize the typical applications of various types of extrusion grades and molding grades of PVC, respectively [42].

Table 6.10 details the medical applications of various PVC materials and blends.

6.3 Polyethylene (PE) Polyethylene is used in a wide variety of applications, ranging from packaging films, tubing, and IV components to hip and joint replacement implants. Polyethylene exists in various forms (Figure 6.11). Low-density polyethylene (LDPE)

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

85

Table 6.10 Medical Applications of PVC Application

Requirements

Material

Tubing

Clarity

Flexible PVC

Colorability Flexibility Kink resistance Chemical and lipid resistance Biocompatibility EtO, gamma sterilization Thin- to thick-wall tubing Range of hardness Lubricity Extrusion processability Gloves

Puncture resistant

Flexible PVC

Tear resistant Chemical resistance Fluid barrier properties Nontoxic and nonirritating Toughness and elongation Processable Collection bags

Clarity

Flexible PVC

Flexibility Puncture and tear resistant Burst strength Chemical resistance Low temperature flexibility Nontoxic Sealability/weldability Leak proof Oxygen and moisture barrier Film block resistance Gamma sterilization Blood therapy

Clarity

Flexible PVC

Flexibility Puncture and tear resistant Hemocompatibility Low temperature flexibility Processability in thin-wall films Nontoxic (Continued )

86

PLASTICS

IN

MEDICAL DEVICES

Table 6.10 (Continued) Application

Requirements

Material

Sealability/weldability Leak proof Oxygen and moisture barrier Gamma sterilization Water drain pipes in hospitals

Strength and toughness

Rigid PVC

Durability Corrosion resistant Luer connectors and Y-sites

Moldability

Rigid PVC

Stiffness and strength Dimensional stability Colorability EtO or gamma sterilization Durability Catheters

Flexibility

Flexible PVC

Biocompatibility Hemocompatibility Nontoxic Durability EtO or gamma sterilization Dimensional stability Contamination free Extrusion processability MRI fixtures and receiving coils

Toughness, impact resistance, low interference, durability

PVC/SAN

Medical instrument components and parts

Flame retardance

PVC/SAN, PVC, ABS, PVC/ c-PVC

Impact resistance Cleanability Processability

Packaging

Clarity

Flexible PVC

Film strength and toughness Puncture and tear resistant EtO, gamma sterilization Barrier properties Extrusion processability Drip chambers

Clarity

Rigid PVC

Dimensional stability Chemical resistance Hemocompatibility (Continued )

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

87

Table 6.10 (Continued) Application

Requirements

Material

Impact resistant Moldability Oxygen face masks

Clarity

Flexible PVC

Comfort Toughness and strength Reasonable stiffness Dimensional stability Nonirritating Nontoxic

contains many long-chain branches along the polymer backbone, preventing the alignment and packing of the chains and thus forming a low-density material. Linear low-density polyethylene (LLDPE) contains several short chains along the polymer backbone. The short chains prevent the alignment and packing of the polymer chains, but the chains are mostly linear. High-density polyethylene (HDPE) contains about 4-10 short chains along the polymer backbone. The relatively few side chains allow the polymer backbone to align and pack together to form a crystalline, high-density plastic. Ultrahigh molecular weight polyethylene (UHMWPE), as the name suggests, is a linear polyethylene with low short chains along the polymer

backbone with a very high molecular weight. Molecular weights range from 2 to 6 million. The high molecular weights provide superior strength, stiffness, and durability compared to the other types of polyethylenes. The physical and chemical properties of each of these materials are compared qualitatively in Table 6.11.

6.3.1 Polyethylene Manufacture Polyethylene is produced by polymerizing ethylene under high pressures in the presence of free radicals, or under low to medium pressures using catalysts. The free radical, high-pressure process is

LDPE Long Chain Branching Poor packing

LLDPE 10–35 low MW side chains per 1000 carbon atoms Intermediate packing HDPE 4–10 low MW side chains per 1000 carbon atoms Excellent packing

Figure 6.11 Schematic structures of various types of polyethylenes.

88

PLASTICS

IN

MEDICAL DEVICES

Table 6.11 Advantages and Disadvantages of Various Polyethylenes Polymer

Advantages

Disadvantages

LDPE

Excellent chemical resistance

Low tensile strength

Very flexible, with good fatigue resistance and toughness

Very difficult to bond or print on

Very good dielectric properties

Susceptible to environmental stress cracking

Tasteless, odorless, meet FDA requirements Low moisture permeability; corrosion resistance; high flexibility; chemically inert; high impact strength; tear and stress crack resistance; high clarity; radiation resistance HDPE

Excellent chemical resistance

Very difficult to bond or print on

Very good dielectric properties

Self-extinguishing grades have low physical properties

Highest rigidity among PEs Good toughness and impact resistance Nontoxic Nonstaining Easily molded and extruded UHMWPE

Excellent wear and abrasion resistance; excellent chemical resistance; excellent environmental stress cracking resistance

Poor processability compared to the lower-molecular-weight PEs

Ethylene copolymers

Very flexible

Low tensile strength

Very good toughness and resiliency Excellent chemical resistance Tasteless, odorless, meets FDA requirements Good flex cracking and environmental stress cracking resistance

Some loss of inherent ethylene solvent resistance

High filler loading capacity

used mostly for the production of LDPE, using oxygen or peroxides as catalysts. The highly branched polymer (Figure 6.11) is the result of the uncontrolled free radical polymerization where free radicals at the end of the propagating polymer chain can “backbite” on itself to generate branches of different lengths. The branched polymer does not align and pack well, resulting in lower crystallinity and hence a lower density (Table 6.12). Linear low-density polyethylene is a linear polymer with a significant number of short chain branches. This polymer is obtained by the

copolymerization of ethylene with highermolecular-weight alpha-olefins like butane, hexane, and octane (Figure 6.12). HDPE is produced either in a slurry process or a gas phase process. In the Phillips process, ethylene is passed through a slurry of a hydrocarbon solvent (e.g., cyclohexane) containing a catalyst like chromium oxide or aluminum oxide. The resulting polymer is precipitated and purified from the slurry and typically has a molecular weight of about 50,000 Daltons. In the Ziegler process, ethylene is passed through a slurry of hydrocarbon solvent containing

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

89

Table 6.12 Comparison of the Physical and Mechanical Properties of Various Polyethylenes Property

Units

LLDPE

LDPE

HDPE

UHMWPE

Molecular weight

kg/mol

# 600

# 600

200 500

3,000 6,000

Density

g/cc

0.92

0.91 0.93

0.94 0.97

0.93 0.94

Melting point



C

120 125

100 110

130 135

130 140

Glass transition temperature



C

2110

2110

290

2160

HDT at 0.46 MPa or 66 psi



C

45

40 50

80 90

65 75

HDT at 1.8 MPa or 264 psi



C

35

30 40

38 50

42 49

Tensile strength

MPa

11

8 15

18 30

20 25

Elongation @ break

%

300 900

90 800

20 500

300 500

Flexural modulus

GPa

0.15

0.25

0.8 1.25

0.5

Impact strength, notched

J/m

50 1,000

No break

50 100

No break

SD55

SD48

SD68

RR60

30 40%

40 50%

60 80%

60 75%

Surface hardness % Crystallinity

%

RO-OR

+

R

H2C

Initiation

R

Propagation

R

Propagation

R

CH2

CH2

Ethylene R

CH2

+

n H2C

CH2

CH2 n

CH2

R

+

Termination

H2C

n

R n

Polyethylene

Figure 6.12 Polyethylene free radical polymerization.

Ziegler Natta catalysts, which are typically comprised of titanium tetrachloride and triethyl aluminum in an inert (nitrogen) atmosphere. The complex formed between the two catalysts allows the controlled polymerization of ethylene (Figure 6.13), resulting in linear polymer chains with a very low number of ethyl side groups (5 7 per 1,000 carbon atoms). The polymer is removed, precipitated, and purified. In the gas phase process, also known as the Union Carbide process [43], ethylene is polymerized in the gas phase at very high pressures and elevated temperatures using

proprietary catalysts. The solid polymer particles form a bed in the reactor, where gaseous ethylene is the fluidizing agent. The polymer can be used as is because no solvents were used. The linear polymer is able to pack into crystallites, resulting in a more translucent or opaque material with higher crystallinity, excellent chemical resistance, stress crack resistance, and strength. Newer catalyst technologies like metallocenes (Figure 6.14) allow for the production of stereoregular, high-molecular-weight polyethylene (with molecular weights of at least 3 million) with very

90

PLASTICS

C2H5

IN

MEDICAL DEVICES

C2H5 CH3

Al

Cl

CH2

+ Cl

Ti

Cl

CH3 R

Al R

CH2

Ti

Cl

Cl

Cl Cl

Cl

H3C

C2H5

CH2

C2H5 Al

CH3

Al

R

CH

CH

R

CH Cl Cl

Ti

Cl

Cl

Cl

Ti Cl Cl

Cl R

Repeat many times

R

C2H5 Al CH Cl

n

Ti Cl

Cl Cl

R=H Polyethylene R = CH3 Polypropylene

Figure 6.13 Polymerization of polyethylene with Ziegler-Natta catalysts.

few side chains along the backbone and little or no impurities [44 47]. Figure 6.15 shows the basic mechanism of a metallocene-catalyzed polymerization of an alkene. Methylaluminoxane (MAO) is used as a co-catalyst. MAO forms a complex with the metallocene catalyst, creating active sites upon which the rapid polymerization of the alkenes occurs. MAO increases the reactivity by 10,000

[48]. These materials are highly crystalline and possess excellent strength and toughness compared to polyethylenes produced in the conventional way. Ultrahigh molecular weight polyethylene produced by this method, is used in orthopedics (hip and knee implants) and as sutures. Polyethylene copolymers with tailored microstructures and molecular weight also can be made using metallocene catalysts.

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

its higher crystallinity, it has better chemical resistance, stiffness, and strength than LDPE. Surgical and medical instruments use the vast majority of HDPEs. Like LDPE, HDPE exhibits good chemical and stress crack resistance, radiation resistance, and impact strength. High-density polyethylene (HDPE) is widely used in medical tubing, where its low cost, low friction, chemical resistance, and easy moldability make it a strong competitor to PVC. Another HDPE market is pharmaceutical closures. Ultrahigh molecular weight polyethylene (UHMWPE) possesses exceptional impact strength, low wear, stress crack resistance, and excellent energy absorption—features that make it an ideal material for use in sutures and artificial hip, knee, and shoulder joints. The physical and mechanical properties of polyethylene are compared in Table 6.12.

R

Cl Cl

M

X

Cl

Zr

91

Cl R

Figure 6.14 Structures of metallocene catalysts.

6.3.2 Polyethylene Properties Low-density polyethylene has a good balance of flexibility, strength, barrier properties, and cost and can have a wide combination of properties. Low-density polyethylene has high clarity, is chemically inert, and has good impact strength and excellent tear and stress crack resistance. Low-density polyethylene (LDPE) has applications in sterile blister packs for drug packaging. Linear low-density polyethylene (LLDPE) is used in films and packaging due to its flexibility and toughness. High-density polyethylene (HDPE) is typically translucent and less flexible than LDPE. Due to

6.3.3 Polyethylene Chemical Resistance Polyethylene exhibits excellent chemical resistance to most chemicals or disinfectants used in

R Me ZrCl2

+

MAO

Me

Zr Step 1

Zr

R

Step 2

MAO - Methyl aluminoxane cocatalyst Step 1 - MAO complexes with zirconene to form active site Step 2 - Alkene co-ordinates with the catalyst Step 3 - Alkene is inserted into the catalyst creating new active site Step 4 - Repetition of step 3 Steps 3 and 4 repeat several thousand times per second High molecular weight stereoregular polymer is formed

R Steps 3 & 4

R

n

R

R

Zr n

R = H Polyethylene R = CH3 Polypropylene

Figure 6.15 Mechanism of polymerization of alkenes with a metallocene catalyst.

Me

92

PLASTICS

hospitals and clinics. It is also resistant to most hydrocarbon solvents. Cyclic ethers like tetrahydrofuran (THF) and chlorinated hydrocarbons like methylene chloride will attack the polymer, causing it to swell and deform (Table 6.13). The higher crystallinity (and thus lower amorphous content) of high-density polyethylene makes it chemically more resistant than low-density polyethylene, which has a lower crystallinity (and thus higher amorphous content). The higher amorphous content of Low-density polyethylene allows chemicals, solvents, and gases to diffuse into the material, causing it to swell or completely dissolve. Organic solvents like cyclic ethers and chlorinated hydrocarbons can cause environmental stress cracking, especially if there is high molded-in stress due to improper processing of the polyethylene part or component [49].

6.3.4 Polyethylene Sterilization The low heat deflection temperatures of polyethylenes (30 50 C) make them unsuitable for steam and autoclave sterilization because the plastics would bend, warp, and deform under the temperatures (100 130 C) used in such methods (Table 6.14). Polyethylenes are suitable for ethylene oxide, gamma radiation, and e-beam sterilization. Those materials containing phosphite stabilizers may

IN

MEDICAL DEVICES

yellow. Ethylene oxide has no effect on the properties of high-density polyethylene, as shown in Figure 6.16 [50]. Polyethylene will oxidize or cross-link under high-energy radiation and needs to be stabilized to reduce this phenomenon [51,52]. The level of surface oxidation can be determined by the analysis of carbonyl and hydroxyl groups that are formed during oxidation (Figure 6.17) [53]. In some cases, UHMWPE is deliberately crosslinked to improve the wear behavior in knee and hip implants. This cross-linking is done before machining the part. In order to get cross-linking, and to minimize the degradation due to chain scission and oxidative degradation, the irradiation and postheat treatment are optimized so that the top layer of the material is oxidized and the internal sections are cross-linked during the process. The parts are then machined to form the acetabular cups. The machining removes the oxidized top layer, leaving a cross-linked, wear-resistant part. Radiation doses of 50 100 kGy are used for crosslinking and standard doses of 25 40 kGy (in an inert atmosphere) are used to sterilize the part. Ethylene oxide or steam sterilization also may be used. After the cross-linking irradiation, the parts are generally heat treated to quench any free radical still present in the material. Several comparative

Betadine

Lipids

Soaps/ Detergents

Disinfectants

Hydrogen Peroxide

Bleaches

Saline Water

Silicones

Oils/Greases

Ethylene Oxide

IPA

Acetone

MeCL2

MEK

THF

Dilute Basses

Polymer

Dilute Acids

Table 6.13 Chemical Resistance of Polyethylenes

Polyolefins HDPE

Good Good Poor Good Poor Good Good Good Good Good Good Good Good Good Good Good Good

LDPE

Good Good Poor Fair Poor Good Good Fair

UMHPE

Good Good Fair Good Fair Good Good Good Good Good Good Good Good Good Good Good Good

Fair Good Good Good Good Good Good Fair Good

Table 6.14 Sterilization of Polyethylenes Polymer

Steam

Dry Heat

Ethylene Oxide

Gamma Radiation

E-Beam

HDPE

Poor

Poor

Good

Good

Good

LDPE

Poor

Poor

Good

Good

Good

UMHPE

Poor

Poor

Good

Good

Good

Polyolefins

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

93

Effect of EtO Sterilization on HDPE Percent Property Retention

107% 106% 105% 104% 103% 102% 101% Tensile Strength @ Break Elong. @ Break

100% 99% 0

0.5

1

1.5

2

2.5

3

3.5

Number of Cycles

Figure 6.16 Effect of ethylene oxide sterilization on the properties of polyethylene.

Effect of Gamma Radiation on PE Stability (0.18% Antioxidant used for stabilized PE) 80

Concentration (104 mol/l)

70 60 Virgin PE - Carbonyl conc. 50

Virgin PE - Hydroxyl conc.

40

Stabilized PE - Carbonyl conc.

30

Stabilized PE - Hydroxyl conc.

20 10 0 0

10

20

30

40

50

60

Radiation Dose (kGy)

Figure 6.17 Surface oxidation of polyethylene during gamma radiation.

clinical and in vitro wear studies made on conventional and cross-linked UHMWPE have shown a better wear behavior for the latter, in spite of a decrease in other mechanical properties such as fatigue strength, as shown in Figure 6.18 [54 56]. Additives like phenolics and vitamin E are used to stabilize polyethylene [57 59]. Several studies have been conducted on the wear of UHMWPE. This is because this material is used in hip and knee replacements in acetebular cups. The material must be able to maintain its dimensions and properties over a long period of

implantation and must be wear resistant when rubbing against the metal alloys of the device assembly. Figure 6.19 shows one study that determined the amount of wear of UHMWPE on both unaged and aged samples [60]. The ethylene oxide sterilized material showed slightly better wear properties than the gamma-sterilized product after aging. Such wear has not been any cause for concern; hundreds of thousands of implant procedures have been conducted with no adverse effects. Surface cross-linked UHMWPE exhibits better wear than noncross-linked UHMWPE [61].

94

PLASTICS

IN

MEDICAL DEVICES

Effect of High Doses of Gamma Radiation on UHMWPE 800

60 Elongation (%) Maximum Strength (Mpa)

50

600 Elongation (%)

40 500 400

30

300 20 200 10 100 0 0

50

100

150

200

250

Radiation Dose (kGy)

Figure 6.18 Effect of gamma radiation on the properties of polyethylene.

a

Wear of Sterilized UHMWPE (unaged)

Volumetric Wear (mm3)

250 200

EtO Sterilized UHMWPE Gamma Sterilized UHMWPE

150 100 50 0 1

2 Number of cycles (millions)

Volumetric Wear (mm3)

b

Wear of Sterilized UHMWPE (aged) 250 200

EtO Sterilized UHMWPE Gamma Sterilized UHMWPE

150 100 50 0 1

2

3

Number of Cycles (millions)

Figure 6.19 Wear of UHMWPE after gamma radiation and aging. (a) Unaged; (b) aged.

0 300

Maximum Strength (MPa)

700

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

6.3.5 Polyethylene Biocompatibility Polyethylenes are inert, biocompatible, and nontoxic [62,63]. However, oxidation of the surface during radiation sterilization can affect the biocompatibility [64], so sterilization should be conducted in an inert atmosphere in order to maintain the inertness of the surface. Biocompatibility studies for UHMWPE showed that the material was biocompatible. The material was evaluated using system toxicity, sensitization, cytotoxicity, mutagenicity, and direct contact hemolysis and thrombogenicity tests [65]. The results are summarized in Table 6.15. In a final report on the safety assessment of polyethylene, the Cosmetic Ingredient Review Expert Panel has concluded that polyethylene is not toxic and does not pose any threat via its use in cosmetics and medical devices [66]. The review evaluated several papers and studies that included toxicity and biocompatibility tests, including those from the ISO 10993 standards.

6.3.6 Polyethylene Joining and Welding Polyethylene can be welded by various techniques like vibration, ultrasonic, friction, hot gas, and hot plate welding. LDPE is easier to weld than HDPE. Most adhesives can be used with polyethylene. It is important to clean the surfaces well before applying the adhesives.

6.3.7 Polyethylene Applications— Examples Table 6.16 lists some of the properties of the medical device applications of polyethylene.

95

6.4 Polypropylene (PP) High clarity, good barrier properties, and radiation resistance make polypropylene very useful in medical devices and packaging. Manufacturers of medical-grade polypropylene often position it and its copolymers with ethylene as a competitor to PVC, glass, and other plastics. Typical healthcare applications of polypropylene include blister packs, flexible pouches, syringes, tubing, hospital disposables, test tubes, beakers, and pipettes. In medical products, polypropylene can be blown or cast into films, as well as coextruded with other materials for a range of performance and barrier properties. The structures of polypropylene are shown in Figure 6.20. In isotactic polypropylene (i-PP), the methyl groups are on the same side of the polymeric carbon chain. Isotactic polypropylene is the most commercially useful polymer. In syndiotactic polypropylene (s-PP), the methyl groups alternate sides. In atactic polypropylene (a-PP), the methyl groups are randomly distributed along the polymer chain. These structural differences lead to various physical and mechanical properties of the polymers. For instance, atactic polypropylene has little or no use commercially, and syndiotactic polypropylene is difficult to manufacture and is cost prohibitive commercially. Most commercially available polypropylene is isotactic. Table 6.17 details the qualitative differences among the three polymers.

6.4.1 Polypropylene Manufacture Commercial polypropylene is manufactured by a catalytic polymerization process. The free radical process is inefficient, with poor yields, and produces a low-molecular-weight, amorphous, oily,

Table 6.15 Biocompatibility of UHMWPEs Test

Comment

System toxicity

No toxic signs observed during the 72-h period of treatment

Sensitization

No toxic signs observed

Cytotoxicity

Extracts showed no reactivity (no cell lysis with discrete intracytoplasmic granules)

Mutagenicity

No mutagenic activity was observed with the extract samples of UHMWPE, with and without metabolic activation

Hemolysis

UHMWPE exhibited ,1% hemolysis

Thrombogenicity

The clotting times for UHMWPE were the same as that of the negative control. The positive control had a sevenfold increase in clotting time compared to the negative control

96

PLASTICS

IN

MEDICAL DEVICES

Table 6.16 Medical Device Applications of Polyethylenes Application

Requirements

Material

Packaging

Clarity

LDPE

Puncture and tear resistance Strength Barrier properties Gamma sterilization Filters

Purity

HDPE

Durability Filterability Arthroscopy sutures

High strength

UHMWPE

Biocompatibility Lubricity High strength Flexibility and toughness Excellent tensile and breaking strength Abrasion resistance Light weight Thin and strong Tubing

Clarity

LDPE, LLDPE

Flexibility and kink resistance Biocompatible Chemical resistance Processability IV fluid bottles, single-dose ampoules

Clarity

LDPE

Toughness and impact resistance Sterilization (steam up to 110 C, EtO, gamma) No leachables

Open-jaw slide clamp for drug delivery systems

High strength and toughness

HDPE

Durability Injection moldable Gamma sterilization

Caps for luers and bottles

Flexibility and toughness

LDPE

Chemical resistance Gamma sterilization Colorability Processable Acetabular joint

Strength

UHMWPE

Toughness (Continued )

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

97

Table 6.16 (Continued) Application

Requirements

Material

Abrasion resistant Biocompatible Durable Chemically inert Gamma sterilization Underpads for hospital beds

Barrier properties

LDPE

Chemical resistance High coefficient of friction Processability Sutures

Strength

UHMWPE

Biocompatibility Nontoxic Lubricity Durability Chemical resistance Hemocompatibility Purity; low contamination Gamma sterilization Heart valves

Wear resistant

UHMWPE

Excellent fatigue strength Biocompatible Mechanical durability Toughness and strength Dimensional stability Gamma sterilization

Atactic Polypropylene

Syndiotactic Polypropylene

Isotactic Polypropylene

Figure 6.20 Polypropylene structures.

Table 6.17 Comparison of Atactic-, Syndiotacticand Isotactic-Polypropylenes a-PP

s-PP

i-PP

Amorphous, elastomeric, lower HDT

High clarity

Semicrystalline, more dense, higher chemical resistance

More ductile than i-PP

Higher melting point, higher tensile strength, higher stiffness, (MW 200,000 600,000)

Exhibits thermoplastic elastomeric behavior

98

PLASTICS

RO-OR

Initiation

IN

MEDICAL DEVICES

R

CH3

+

R

H2C

CHCH3

Propagation

R

CH

Propylene

CH3

CH3 R

CH

+

Propagation

n H2C

R

CHCH3

CH2 n

CH3 R

CH3

CH3 CH

+

Termination

H2C R

n

n

Polypropylene

Figure 6.21 Basic polymerization mechanism of polypropylene.

and waxy polypropylene. Recent advances in catalyst technology enable the manufacture of stereoregular, high-molecular-weight polypropylene that has a high degree of order and crystallinity. The basic mechanism of polypropylene polymerization is shown in Figure 6.21. Ziegler-Natta catalysts are used commercially to produce high-molecular-weight isotactic-polypropylene [67]. These catalytic systems comprise an organometallic compound like triethyl aluminum and a transition metal compound like titanium trichloride. A reaction between the two catalysts produces radicals, which propagate the polymerization. The structure of the catalyst allows the propylene monomer to coordinate with the catalyst and polymerize stereospecifically and sequentially producing high-molecular-weight isotactic-polypropylene (Figure 6.13). Newer gas-phase polymerizations produce high yields of isotacticpolypropylene with more than 97% purity. Metallocene catalysts can be used to produce various types of polypropylenes (atactic, isotactic, or syndiotactic) with great control and stereospecificity [68,69]. Metallocene catalysts are compounds of cyclopentadiene or other polyaromatic compounds and a metal, typically zirconium or hafnium (Figure 6.22). These catalysts exhibit high selectivity and reactivity to olefin polymerizations. For example in Figure 6.22, catalyst 1 will produce atactic-polypropylene, catalyst 2 will produce

isotactic-polypropylene, and catalyst 3 will produce syndiotactic-polypropylene [70,71]. Commercial polypropylenes produced with metallocene catalysts show superior transparency compared to conventional polypropylene due to the formation of crystallites that are smaller than the wavelength of light. They also have an extremely narrow molecular weight distribution, leading to reduced levels of distortion during injection molding and the potential for the production of dimensionally stable parts.

6.4.2 Polypropylene Properties The advantage of polypropylene is that it is strong, relatively rigid, and lightweight. The polymer retains most of its mechanical properties at elevated temperatures and has a high performance-tocost ratio. It has good chemical and stress crack

CI M

CI M

CI CI

CI

CI

1, M = Zr, Hf

M

2, M = Zr, Hf

3, M = Zr, Hf

Figure 6.22 Metallocene catalysts used for the polymerization of various types of polypropylene.

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

resistance, is autoclavable, and has excellent dielectric properties. Polypropylene becomes brittle at low temperatures (typically below 232 C) and is not weather or radiation resistant unless additives and impact modifiers are compounded into it. Clear grades are also available. Table 6.18 compares the properties of the various types of polypropylene. Of the three varieties, isotactic-polypropylene is the most widely used in medical device applications. The demand for polypropylene continues to grow, especially with recent advances in manufacturing and polymerization. The current stiffness of unfilled polypropylene grades (flexural modulus of 2.2 GPa) is much higher than what was available a few years ago (flexural modulus of 1.9 GPa). Higher-stiffness polypropylenes continue to be introduced into the market, with flexural modulus values reaching 2.5 GPa. This allows the design of thinner walls and can reduce cycle times and cost of production. Resins that combine high stiffness, high clarity, and high gloss are also available and are especially good for packaging, drug delivery components, and labware.

6.4.3 Additives for Polypropylene Several additives are used to enhance the properties of virgin polypropylene. Clarifiers and nucleating agents enable the tailoring of properties for a wide range of applications. Nucleating agents like talc, sorbitols, and metal phosphates increase the crystallinity, and hence the stiffness and chemical

99

resistance, of polypropylene [72]. Nucleating agents particularly effective in polypropylene plastics are benzoate salts of sodium, potassium, and aluminum, and sorbitols such as bis-benzylidene sorbitol and bis (p-methoxy benzylidene sorbitol). These are relatively volatile materials and are added at typical concentrations of about 0.5%. Less volatile and effective sorbitol-nucleating agents have also been developed. Sorbitols are soluble in the propylene matrix. When the molten polymer cools, the sorbitols crystallize into nanometer scale crystallites that act as nucleating sites, resulting in the formation of very small polypropylene crystallites. The crystallites are smaller than the wavelength of light, rendering the part or film clear and transparent while still maintaining strength and toughness. These are especially advantageous for packaging and drug delivery applications. Nucleating agents reduce cycle times during molding and increase throughput and productivity. Clarifying agents (a subclass of nucleating agents), like sorbitol dibenzyl acetates, improve the clarity and transparency of polypropylene grades and also improve processability. Some of the advantages of nucleated polypropylene include the following:

• • • • •

Increased crystallization speed and temperature, Higher dimensional stability, Increased stiffness, Higher heat resistance, and Higher transparency.

Table 6.18 Properties of Polypropylenes



Property

Units

a-PP

s-PP

i-PP

Density

g/cc

0.86

0.9

0.905

Haze

%

70

2

10

Melting point



C

—

168

163

Glass transition temperature



C

220

28

210

HDT at (0.46 MPa or 66 psi)



C

—

—

100

HDT at (1.8 MPa or 264 psi)



C

—

—

55

Softening point



C

90 150

—

—

Tensile strength

MPa

0.8

61

30 35

Elongation @ break

%

.1,000

—

100 300

Flexural modulus

GPa

—

1.0 1.3

1.5 2.0

Impact strength, notched

J/m

—

—

50 120

% Crystallinity

%

5 10

30 40

40 60

Most commercially available PPs are isotactic.

100

PLASTICS

Due to the presence of a tertiary, labile hydrogen atom on the polymer chain, polypropylenes, and their copolymers are prone to oxidation and degradation (Figure 6.23). Antioxidants are necessary to prevent oxidation and degradation of the polymer. Phenolic, hindered amine, and phosphate antioxidants are used at typical concentrations of 0.01 0.5% [73]. Thioethers are also used and provide synergistic effects when combined with one of the phenolics.

6.4.5 Polypropylene Sterilization The heat distortion temperature (HDT) of isotactic-polypropylene is 100 C and can be sterilized by steam sterilization and autoclaving using a limited number of cycles (Table 6.20). Newer grades with higher heat resistance can withstand steam and autoclave sterilization temperatures. Steam sterilization showed no decrease in crystallinity and physical properties [74]. Ethylene oxide also can be used for the sterilization of polypropylene. No significant changes in properties were observed when polypropylene was sterilized with ethylene oxide after one and three cycles [50], as shown in Figure 6.24. Polypropylene must be stabilized with free radical scavengers to prevent degradation and discoloration when exposed to high-energy radiation. Highenergy radiation forms free radicals on the tertiary hydrogen of polypropylene (Figures 6.23 and 6.25). The polymer chains can either unzip and degrade

Polypropylene exhibits excellent chemical resistance to most solvents, disinfectants, lipids, and bleaches. Applications for drug delivery, luer components, connectors, syringes, and labware take advantage of the clarity and chemical resistance of the polymer. Polypropylene is resistant to many polar liquids such as alcohols, organic acids, esters, and ketones. Aliphatic, aromatic, and halogenated hydrocarbons will swell polypropylene (Table 6.19). The extent of swelling will depend upon the percentage of crystallinity (the less crystalline and more amorphous the material, the greater the swelling). Polypropylene is resistant to most aqueous solutions (salts, acids, and bases). However, strong oxidizing agents and very strong acids will attack CH3

MEDICAL DEVICES

polypropylene at room temperature. Environmental stress cracking is not common with polypropylene because it is a semicrystalline polymer. polypropylene copolymers have lower crystallinity than polypropylene homopolymers and are thus more susceptible to attack by certain types of chemicals.

6.4.4 Polypropylene Chemical Resistance

CH3

IN

CH3

CH3

CH3

CH3

R

+

Free Radical or High heat n

RH

n

H

Labile Hydrogen

Polymer oxidation and/or degradation

Figure 6.23 Free radical formation in polypropylene.

Betadine

Lipids

Soaps/ Detergents

Disinfectants

Hydrogen Peroxide

Bleaches

Saline Water

Silicones

Ethylene Oxide Oils/Greases

IPA

Acetone

MeCL2

MEK

THF

Dilute Basses

Polymer

Dilute Acids

Table 6.19 Chemical Resistance of Polypropylenes

Polyolefins PP

Good Good Fair Good Fair Good Good Fair Good Good Good Good Good Good Good Good Good

PP copolymers

Good Good Poor Fair Fair Good Good Fair Fair Good Good Good Good Good Good Fair Good

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

101

Table 6.20 Sterilization Capability of Polypropylenes Polymer

Steam

Dry Heat

Ethylene Oxide

Gamma Radiation

E-Beam

HDPE

Poor

Poor

Good

Good

Good

LDPE

Poor

Poor

Good

Good

Good

UMHPE

Poor

Poor

Good

Good

Good

Good

Fair

Good

Fair

Fair

Good

Fair

Good

Fair

Fair

Fair

Fair

Good

Good

Good

Polyolefins

PP

a

PP copolymers COC a

Radiation stable grades should be considered for gamma and e-beam radiation sterilization.

Effect of EtO Sterilization on PP Percent Property Retention

120% 100% 80% 60% 40% Tensile Strength @ Break Elong. @ Break

20% 0% 0

0.5

1

1.5

2

2.5

3

3.5

Number of cycles

Figure 6.24 Effect of ethylene oxide sterilization on the properties of polypropylene.

or oxidize and discolor (yellow). A schematic is shown in Figure 6.25. Additives that absorb the radiation or scavenge the free radicals are used to stabilize polypropylene for gamma and e-beam radiation applications [75 77]. The stability of polypropylene after exposure and accelerated aging at 80 C is shown in Figure 6.26 [78]. A stabilized polypropylene maintains close to 80% of its properties even after nine weeks, compared to an unstabilized, standard polypropylene that loses 80% of its properties after nine weeks. Figure 6.27 shows that the physical properties of a stabilized polypropylene (using a hindered amine stabilizer) are significantly better than an unstabilized polypropylene after exposure to gamma radiation doses of 26 kGy and 50 kGy [79].

6.4.6 Polypropylene Biocompatibility Commercial polypropylene biocompatible grades are available. Applications that require biocompatibility

include heart valve structures, wound dressings, and catheters. Polypropylene mesh has been used with good results in general surgery, as well as in plastic reconstructive, urological, gynecological, and thoracic surgeries. Polypropylene meshes are also used in hernial repair operations. Several studies on the biocompatibility of polypropylene meshes have been conducted and have shown that polypropylene exhibits no adverse effects and is biocompatible [80 83].

6.4.7 Polypropylene Joining and Welding Thermal bonding or welding techniques typically work well for polypropylene. Such methods include hot gas welding, heated tool welding, friction welding, and vibration welding. Other techniques that can be used include infrared welding, ultrasonic welding, and heat sealing. The type of polymer (homopolymer or copolymer), its characteristic

102

PLASTICS

CH3

CH3

CH3

IN

MEDICAL DEVICES

CH3

Oxidation Products O O

O2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

Radical Formation

+ ROH

H RO

Chain Scission

CH3 Continued radical formation and chain scission leading to polymer degradation

CH3

CH3

CH3 +

Figure 6.25 Degradation and oxidation of polypropylene when exposed to high-energy radiation.

Percent Charpy Impact Retention (%)

Gamma Radiation Stability of PP after Aging (Radiation Dose 38 kGy) 120% Standard PP Stabilized PP

100% 80% 60%

40% 20% 0% Control

0

1

3

7

9

Aging Time (weeks)

Figure 6.26 Properties of stabilized and unstabilized polypropylene after exposure to gamma radiation and aging at 80 C.

(percent crystallinity), and filler content will determine the most effective welding method.

6.4.8 Polypropylene Applications By far, the most popular application of polypropylene is in the production of disposable hypodermic syringes that use clear, radiation-resistant

polypropylene. Both syringe plungers and barrels are made from polypropylene. Other applications include medical tubing and bags, connectors and kits, trays, labware, beakers, vials and containers, collection cups, and packaging. The clarity, chemical resistance, toughness, and strength of polypropylene make it an excellent material for labware applications that include centrifuge tubes, pipette

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

103

Stability of Polypropylene after Gamma Radiation Bending Test - Days to Failure

400 Standard PP

350

Stabilized PP 300 250 200 150 100 50 0 25

50

Radiation Dose (kGy)

Figure 6.27 Physical properties of stabilized and unstabilized polypropylene after exposure to gamma radiation.

tips, multiwell plates, diagnostic cuvettes, containers, and sample cups. An emerging market for polypropylene, particularly in Europe, is parenteral nutrition and dialysis films. Polypropylene can also be spun into fibers and thus finds applications in sutures and medical apparel. One of the major applications for polypropylene in the medical device industry is in nonwoven applications. Polypropylene is converted into nonwoven fabrics by several processes that produce very fine, highly oriented fibers that are deposited onto a random mat. Nonwoven fabrics and shapes are formed by processes like spin bonding and melt blowing. Such structures include surgical and isolation gowns, drapes, sterilization wraps, face and surgical masks, filters, and meshes. Currently, nonwovens can be found in a wide variety of medical-related areas, including facial masks, surgical packs, gowns and drapes, sterilization packaging, gloves, surgical accessories, and even protective footwear and hoods. Nonwoven fabrics are produced by alternative methods to conventional knitting or weaving. Raw materials such as fibers, filaments, or yarns are bonded together through heating, mechanical means, solvent application, or chemical processes. The bonding technology and the type of material employed influence the specific properties of the finished nonwovens. In general, the fabrics are grouped according to the processing methods. Airlaid pulp, dry-laid, needlepunched, spunbonded, spunlaced, and wet-laid comprise the major types of nonwovens. Most enduse medical disposables are produced by spunbonded or wet-laid techniques.

Spunbonded (or spunlaced) nonwovens are composed of polymer-based fibers that yield a fabric of exceptional strength. The basic process extrudes and forces fibers through a multihole spinneret to create filaments. After a cooling phase, the filaments are randomly drawn along the width of a moving conveyor to create a continuous web. In the final stage, the filaments within the web are locked together by heat or chemicals to form the finished fabric. Spunbonded nonwovens are usually made from polyester or polypropylene fibers and serve a wide range of disposable medical supplies applications, including kit and tray lidding, adult diapers, surgical gowns and single-use towels, and bedding. Table 6.21 details some of the applications and requirements that use polypropylene.

6.5 Cyclo Olefin Copolymers (COCs) Over the last couple of decades, a new class of polymers called cyclo olefin copolymers or cyclic olefin copolymers (COCs) has been introduced. They have made significant inroads in the medical device industry and are being used in lab and diagnostic applications, including the replacement of glass vials, bottles, and ampoules. Cyclo olefin copolymers are amorphous, transparent copolymers of cyclo olefins and linear olefins. They exhibit a combination of high transparency, excellent impact resistance, and improved shatter resistance compared to glass, and superior moisture barrier properties. They also have

104

PLASTICS

IN

MEDICAL DEVICES

Table 6.21 Medical Device Applications of Polypropylene Application

Requirements

Material

Packaging

Steam, EtO, gamma sterilization

Nucleated metallocene polypropylene

High clarity Good oxygen/water barrier Excellent seal integrity Sealability Puncture and tear resistance Pouch

Clarity

Metallocene PP

Low haze Gamma sterilization Puncture and tear resistance Flexibility Excellent burst strength Chemical resistance Low extractables and leachables Processability Drapes and gowns

Mechanical strength

PP nonwoven fibers

Liquid barrier Comfort and soft touch EtO and gamma sterilization Burst strength Tensile strength Being lint-free Chemical resistance Sutures

Strength

PP fibers

Colorability Biocompatibility Hemocompatibility Durability EtO and gamma sterilization Syringes

Clarity Impact strength and toughness Shatter resistance Dimensional stability Chemical resistance No extractables and leachables Burst strength EtO, steam, gamma sterilization

PP

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

excellent electrical properties and improved thermal resistance over polyethylene and polypropylene. Cyclo olefin copolymers offer an excellent mix of optical and mechanical properties compared to other optically clear plastics. They have better transmittance at visible and near-ultraviolet wavelengths and lower birefringence than polystyrene and polycarbonate. Their low moisture absorption provides excellent dimensional stability and processing stability. Their low extractables give them excellent biocompatibility. Cyclo olefin copolymers can be compounded with pigments, lubricants, glass fibers, flame retardants and other additives, and fillers. It can be processed by a range of methods, including injection molding, film, sheet and profile extrusion, and injection blow molding. Drying and other special pretreatments are not needed. Cyclo olefin copolymers have the following characteristics:

• • • • • •

High transparency,

• • • • • • • •

Light weight and low density,

Low optical birefringence, Very low moisture absorption and permeability, High stiffness and hardness and low creep, High strength with low elongation, Higher heat resistance than polyethylene and polypropylene,

105

The use of a comonomer (in this case an olefin like ethylene) produces a polymer with higher heat resistance than a polyolefin. The first ROMP catalysts were discovered in the 1950s [84,85]. Commercially viable cyclo olefin copolymers that could be processed and used in specific industrial applications used the Ziegler Natta catalysts [86,87]. The discovery of metallocene catalysts [44,45] allowed for the commercial production of pure, highmolecular-weight copolymers especially the copolymer of norbornene and ethylene (Figure 6.28). The resulting polymer is a completely saturated polymer with no double bonds.

6.5.2 Cyclo Olefin Copolymer Properties Norbornene is much bulkier than ethylene and has a rigid, bridged-ring structure that prevents crystallization. This compound is incorporated randomly into the main chain, resulting in an amorphous, stiff material with a higher glass transition temperature and a higher heat resistance compared to polyethylene and polypropylene. The thermal properties of the copolymer can be tailored by adjusting the level of norbornene, as shown in Figure 6.29.

+

H2C

CH2

Good dielectric properties, High flow and low shrinkage, Long-term dimensional stability,

Ethylene

Norbornene

High purity with very low extractables, Biocompatibility, Good chemical resistance, and

Metallocene catalyst + Cocatalyst

Excellent processability and flow.

6.5.1 Cyclo Olefin Copolymer Manufacture Cyclo olefin copolymers are manufactured by the copolymerization of a cyclic olefin (e.g., cyclopentene, norbornene) with an olefin like ethylene or propylene. The reaction of polymerizing a cyclo olefin resulting in a polymer is known as ring opening polymerization (ROMP). Pure cyclo olefin polymers have very high melting points (300 450 C) and are very difficult to process. In most cases decomposition occurs before melting.

y

x

Cycloolefin copolymer

Figure 6.28 Synthesis of a cyclo olefin copolyler using norbornene and ethylene.

106

PLASTICS

Table 6.22 lists the typical properties of a norbornene-ethylene COC.

MEDICAL DEVICES

Table 6.22 Typical Properties of a NorborneneEthylene Cyclo Olefin Copolymer

6.5.3 Cyclo Olefin Copolymer Chemical Resistance Being an amorphous polymer, COCs are prone to environmental stress cracking, especially if the material and part have not been processed properly. Such processing parameters include low melt temperatures, incorrect in-mold residence time and pressure, and improper cooling times. Temperature and length of exposure to the chemical also have an influence on the environmental stress crack resistance (ESCR) [88]. Vegetable and animal fats, lipids, and hot water can affect the ESCR of cyclo olefin copolymers. Cyclo olefin copolymers are resistant to most acids and bases. Organic solvents like cyclic ethers and chlorinated hydrocarbons may swell or dissolve the polymer (Table 6.23). Cyclo olefin copolymers resist dimethyl sulfoxide and other polar solvents better than other amorphous thermoplastics.

IN

Property

Units

COC

Density

g/cc

1.01 1.02

Glass transition temperature



C

100 180

HDT at (0.46 MPa or 66 psi)



C

75 170

Processing temperature



C

240 300

Tensile strength

MPa

66

Tensile elongation

%

3 10

Flexural modulus

GPa

3.4

Charpy notched impact strength

kJ/m2

1.7 2.6

Refractive index

1.53

6.5.5 Cyclo Olefin Copolymer Biocompatibility COCs typically have little or no extractables, making them highly biocompatible. COC grades that are USP Class VI and/or ISO 10993 compliant are available.

6.5.4 Cyclo Olefin Copolymer Sterilization Cyclo olefin copolymers can undergo sterilization by gamma radiation, ethylene oxide (Table 6.24). Those copolymers that have a high glass transition temperature and a high heat deflection temperature can undergo steam and dry heat sterilization. Cyclo olefin copolymer grades for steam and dry heat sterilization should be selected appropriately.

6.5.6 Cyclo Olefin Copolymer Joining and Welding COC parts can be solvent bonded with cyclohexane or heptane. Parts also can be bonded with commercially available plastic adhesives using these or similar solvents or with polyurethane adhesives.

Tg versus percent Norbornene 300 250

Tg (c)

200 150 100 50 0 0

10

20

30

40

50

60

70

80

Norbornene (%)

Figure 6.29 Effect of norbornene concentration on the glass transition temperature of the cyclic olefin copolymer.

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

107

COC

Betadine

Lipids

Soaps/ Detergents

Disinfectants

Hydrogen Peroxide

Bleaches

Saline Water

Silicones

Oils/Greases

Ethylene Oxide

IPA

Acetone

MeCL2

MEK

THF

Dilute Basses

Polymer

Dilute Acids

Table 6.23 Chemical Resistance of Cyclo Olefin Copolymers

Good Good Poor Good Poor Good Good Good Poor Good Good Good Good Good Good Good Good

Table 6.24 Sterilization of Cyclo Olefin Copolymers Polymer

Steam

Dry Heat

Ethylene Oxide

Gamma Radiation

E-Beam

COC

Fair

Fair

Good

Good

Good

Ultrasonic welding or friction welding also may be used. High-frequency welding cannot be used.

6.5.7 Cyclo Olefin Copolymers Medical Applications Cyclo olefin copolymers can be used in laboratory and diagnostic devices. These include syringes, vials and ampoules, cuvettes, microtiter plates, test tubes, petri dishes, pipettes, and specialized labware. They are also finding application in needleless injectors, injector pens, and inhalers. Because of their good thermoformability, COCs are also ideally suitable for the production of blister packs. Table 6.25 details some of the applications and their requirements.

6.6 Polystyrene (PS) With its low cost, low density, clarity, dimensional stability, and adaptability to radiation sterilization, polystyrene possesses many attractive features for medical applications. Polystyrene can come in two forms—crystal polystyrene and high impact polystyrene (HIPS). Medical applications of crystal polystyrene include labware such as petri dishes and tissue culture trays. High-impact polystyrene is used in thermoformed products such as catheter trays, heart pump trays, and epidural trays. Both crystal polystyrene and HIPS find uses in respiratory care equipment, syringe hubs, and suction canisters. In labware and packaging for kits and trays, polystyrene is competitive with PVC, polypropylene, and acrylics. Crystal polystyrene resins are glassy and crystal clear and are most often supplied in the form of one-eighth-inch granules. Known as oriented

polystyrene (OPS), they are brittle until biaxially oriented and then become comparatively flexible and durable. Oriented polystyrene is formed by stretching the polystyrene sheet in the transverse direction, which toughens what otherwise would be a more brittle, thin-gauge sheet. Injection molded general-purpose crystal grades are typically used in applications such as cutlery, drink cups, tumblers, medical and diagnostic labware, office accessories, and housewares. Injection molded, high-heat crystal grades are typically used in applications such as medical products, packaging, housewares, office accessories, and compact disc containers. Extruded high-heat crystal grades are consumed in foam sheets (that are used in meat trays, egg cartons, dinnerware, and fast-food packaging), in oriented polystyrene films (which are used mainly in cookie, cake, and delicatessen trays), and in foamboard stock (which is used in insulation for building and construction). High-impact grades of polystyrene are modified with polybutadiene elastomers. High-impact grades typically contain in the range of 6 12% elastomers and medium-impact grades contain about 2 5%. High-impact polystyrene resins have characteristics such as ease of processing, good dimensional stability, impact strength, and rigidity. In recent years, some high-performance grades of high-impact polystyrene resins have come to compete with more costly engineering resins in applications such as appliances and consumer electronics. Injection molded high-impact polystyrene resins are used in applications such as appliances, premium office accessories, consumer products, and toys. Extruded high-impact polystyrene resins are used in applications such

108

PLASTICS

Table 6.25 Medical Application of Cyclo Olefin Copolymers Application

Requirements

Diagnostics

High transparency and clarity

MEDICAL DEVICES

Table 6.25 (Continued) Application

Requirements

Packaging—Easy tear film

Clarity Easy linear tear on opening

High UV transmittance

Flex crack resistance

Low shrinkage

Gamma sterilization

Chemical resistance to aqueous and polar solutions Vials and containers

IN

High clarity Shatter resistance Low extractables Biocompatibility

Bone cement mixer

Glass like clarity Dimensional stability Chemical resistance to PMMA Biocompatibility Gamma sterilization

Water vapor barrier Sterilizability Dimensional stability Light weight Film packaging

Clarity Thermoformability Flexibility

as food packaging, dairy containers, vending and soda fountain cups, lids, plates, and bowls. Polystyrene can come in three different forms. These forms are called atactic polystyrene, isotactic polystyrene, and syndiotactic polystyrene (sPS) (Figure 6.30). Most commercially available polystyrene is atactic polystyrene.

Tear resistance

6.6.1 Polystyrene Manufacture

Sterilizability Water vapor barrier Lab-on-a-chip disc

Clarity Processability Low autofluorescence Excellent UV transmittance Dimensional stability Low surface energy

Prefilled syringes and containers

Clarity Durability, shelf life stability Sterilizable High purity, low extractables Biocompatibility Shatter resistant Processability Light weight (Continued )

Polystyrene is easily manufactured by the free radical polymerization of styrene using free radical initiators (Figure 6.31). Styrene with or without diluents is mixed with a free radical initiator like dibenzoyl peroxide and heated to a temperature of 120 C. Several stages of polymerization results in a polymer dissolved in the monomer or the diluent solution. The unreacted monomer and diluent are flashed off under a vacuum, leaving the highmolecular-weight polystyrene. High-impact polystyrene is manufactured by the inclusion of a rubber like polybutadiene during polymerization. During polymerization, the polybutadiene is encapsulated into the polystyrene. Grafts and partial cross-linking of the butadiene can also take place affecting the final polymer’s properties. Syndiotactic polystyrene (sPS) was first commercialized by Idemitsu Petrochemical Company, Ltd. of Japan and developed jointly with Dow in 1988. Syndiotactic polystyrene (sPS) is a new semicrystalline engineering polymer and is produced by a continuous polymerization process using metallocene catalysts similar to those used for polyolefins.

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

109

Atactic Polystryene

Syndiotactic Polystryene

Isotactic Polystryene

Figure 6.30 Structures of polystyrenes.

Initiation

R

RO-OR

H2C

+

R

CH

Propagation

R

CH

Styrene

R

CH

Propagation

+

n H2C

CH

CH2

R n

CH

R

+

H2C

n

Termination n

Polystyrene

Figure 6.31 Free radical polymerization of polystyrenes.

110

PLASTICS

Like conventional amorphous polystyrene, syndiotactic polystyrene (sPS) is brittle, but it can be reinforced with glass or alloyed with other polymers to improve toughness. Syndiotactic polystyrene (sPS) is extremely chemically resistant and has a high melting point (270 C) and a very low dielectric constant. Its high flow and processing ease make it an excellent candidate for thin-wall applications.

6.6.2 Polystyrene Properties General-purpose or crystal polystyrene is a brittle material. The material can be injection molded and extruded. Injection molding applications include labware, diagnostic equipment, and device components. Extruded grades can be used in trays and packaging. High-impact polystyrene is used in applications like trays, containers, medical components, and packaging. Table 6.26 compares the two types of materials, and Table 6.27 lists some of their properties.

6.6.3 Polystyrene Chemical Resistance Polystyrene is not resistant to aromatic, aliphatic, and chlorinated organic solvents. It is also not resistant to cyclic ethers, ketones, acids, or bases. Polystyrene is moderately resistant to highermolecular-weight aliphatic alcohols, dilute aqueous

IN

MEDICAL DEVICES

acids and bases, and bleach. It is resistant to lowmolecular-weight alcohols, ethylene oxide, and oxidizing and disinfecting agents (Table 6.28). Table 6.26 Comparison of General-Purpose (Crystal) polystyrene and High-Impact Polystyrene General-Purpose (Crystal) Polystyrene

High-Impact Polystyrene

Rigid and hard

Tough; improved impact resistance

Crystal clarity; water white transparency

Translucent to opaque

High gloss

Reduced gloss

Good dimensional stability

Fair dimensional stability

Low water absorption

Reduced water absorption

Good electric and dielectric properties

Reduced electrical properties

Excellent processability

Excellent processability

Excellent gamma radiation resistance

Fair resistance to gamma radiation

Limited chemical resistance

Reduced chemical resistance

Prone to environmental stress cracking

Less prone to environmental stress cracking

Table 6.27 Properties of Polystyrenes Property

Units

General-Purpose Polystyrene

High-Impact Polystyrene

Syndiotactic PS

Density

g/cc

1.05

0.8 1.04

1.02

1.589

—

1.59

Refractive index Melting point



C

—

—

270

Glass transition temperature



C

90 95

85 95

100

HDT at 0.46 MPa or 66 psi



C

85 95

75 85

108

HDT at 1.8 MPa or 264 psi



C

90 100

85 95

90

Softening point



C

75 85

60 110

205

Tensile strength

MPa

40

11 45

45

Elongation @ break

%

1 40

10 100

5 20

Flexural modulus

GPa

3

0.6 3

3.2

Impact strength, notched

J/m

20 50

70 100

60 70

% Crystallinity

%

—

—

60 80

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

111

temperatures will cause the parts to warp and disfigure (Table 6.29). Polystyrene can be sterilized with ethylene oxide. Figure 6.32 shows that the physical

6.6.4 Polystyrene Sterilization Polystyrene is not recommended for steam and autoclave sterilization. Their low heat distortion

Disinfectants

Betadine

Lipids

Soaps/ Detergents

Hydrogen Peroxide

Bleaches

Saline Water

Silicones

Oils/Greases

Ethylene Oxide

IPA

MEK

Acetone

Fair Fair Poor Poor Poor Poor Good Good Fair Fair Good Good Good Good Good Good Fair

MeCL2

Polystyrene

THF

Polymer

Dilute Acids

Dilute Basses

Table 6.28 Chemical Resistance of Polystyrene

Table 6.29 Sterilization of Polystyrene Polymer Polystyrene

Steam

Dry Heat

Ethylene Oxide

Gamma Radiation

E-Beam

Poor

Poor

Good

Good

Good

a

Effect of EtO Sterilization on General Purpose PS

Percent Property Retention

120% 100% 80% 60% 40% Tensile Strength @ Break Izod Impact

20% 0%

0

Percent Property Retention

b

0.5

1

1.5 2 Number of Cycles

2.5

3

3.5

Effect of EtO Sterilization on High Impact PS 120% 100% 80% 60% 40% Tensile Strength @ Break Elong. @ Break

20% 0%

0

0.5

1

1.5 2 Number of Cycles

2.5

3

3.5

Figure 6.32 Effect of ethylene oxide sterilization on polystyrene. (a) Property retention; (b) color stability.

112

PLASTICS

properties of both general-purpose polystyrene and high-impact polystyrene are not significantly affected when exposed to ethylene oxide [50]. Polystyrene is very stable to gamma radiation due to its high aromatic content. The electron clouds are able to absorb the radiation eliminating the generation of reactive free radicals. Polystyrenes can thus be irradiated with several doses of gamma and ebeam radiations. Figure 6.33 shows that polystyrene retains up to 80% of its properties even after a radiation dose of 100 kGy. In addition, there is no significant shift in its color. The initial shift in color after the 100 kGy radiation dose returns close to the original color within a week [89].

IN

MEDICAL DEVICES

polystyrene copolymers are available from specific suppliers.

6.6.6 Polystyrene Joining and Welding It is difficult to weld general-purpose polystyrene due to its brittleness. High-impact polystyrene can be welded using techniques like ultrasonic and radio frequency welding. It can be solvent bonded, although care should be used so as not to cause any environmental stress cracking. Most adhesives can be used with both polystyrene and high-impact polystyrene.

6.6.5 Polystyrene Biocompatibility

6.6.7 Polystyrene Applications— Examples

Polystyrene is typically not used where biocompatibility is a requirement. Biocompatible grades of

Due to its clarity, low cost, and excellent processability, general-purpose polystyrene is used in

a

Effect of Gamma Sterilization on General Purpose PS

Percent Property Retention

120% 100% 80% 60% 40% Tensile Strength @ Break Izod Impact

20% 0%

0

20

40 60 80 Radiation Dose (kGy)

100

120

Color Stability of General Purpose Polystryene after Gamma Sterilization

b

Yellowness Index (YI)

8 7

25 kGy

6

100 kGy

5 4 3 2 1 0

Unexposed

0

1 2 3 4 Time after exposure (weeks)

Figure 6.33 Effect of gamma radiation on polystyrene.

5

6

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

113

Table 6.30 Medical Device Applications of Polystyrene Application

Requirements

Resin Type

Labware and diagnostics (petri dishes, labware, test tubes, IVD products, tissue culture components, flasks, multiwell trays, pipettes, roller bottles)

Transparency

General-purpose polystyrene

Water white clarity Chemical resistance Stiffness Gamma sterilization

Home test kits, diagnostic equipment housings

Toughness

High-impact polystyrene

Opaque Dimensional stability Sterilization trays; surgical instruments; dental equipment

High flow

Syndiotactic polystyrene

Thin walls Dimensional stability Mechanical strength Heat resistance EtO, steam, gamma sterilization

Table 6.31 Commodity Thermoplastics Suppliers Materials

Trade Names

Suppliers

PVC, flexible

Geons

PolyOne Corporation

Alpha PVC CLEAR

AlphaGary

APEXs

Teknor Apex Company

BVC

Bayshore Vinyl Compounds (BVC) Inc.

Colorite

Colorite Polymers

Unichem

Colorite Polymers

Viduxs

Teknor Apex Company

Durals

AlphaGary

Unichem

Colorite Polymers

Alpha PVC CLEAR

AlphaGary

Flexalloys

Teknor Apex Company

VESTOLITs

Creanova, Inc.

PVC, rigid

Poliran KC Rigid PVC

Keysor-Century Corporation

Kydexs

Kleerdex Company

Vinidurs

BASF

Georgia Gulf PVC

Georgia Gulf (Continued )

114

PLASTICS

IN

MEDICAL DEVICES

Table 6.31 (Continued) Materials

HDPE

LDPE

LLDPE

PE copolymers

UHMWPE

Trade Names

Suppliers

Oxy

Occidental Chemical Corp. OxyChem

Roscom

Roscom, Inc.

Superkleens

AlphaGary

Tygon

Saint Gobain—Norton

Bormedt

Borealis A/S

Braskem PE

Braskem

Hostalen

Basell Polyolefins

PRE-ELEC

Premix Thermoplastics, Inc.

Purell

Basell Polyolefins

RIGIDEXs

INEOS Polyolefins

DuPontt 20 Series

DuPont Packaging & Industrial Polymers

AT Series

AT Plastics Inc.

Bormedt

Borealis A/S

CERTENEt

Channel Prime Alliance

J-REX LD

Japan Polyolefins Co., Ltd. (JPO)

Lacqtenes

TOTAL PETROCHEMICALS

Marlexs

Chevron Phillips Chemical Company LLC

Petrothenes

Equistar Chemicals, LP

PRE-ELEC

Premix Thermoplastics, Inc.

Purell

Basell Polyolefins

SABICs LDPE

Saudi Basic Industries Corporation (SABIC)

Samsung Total

Samsung Total Petrochemicals Co., Ltd.

Trithenes

Petroquimica Triunfo

Westlake LDPE

Westlake Chemical Corporation

Novex

INEOS Polyolefins

CERTENEt

Muehlstein

HIFOR Polyethylene

Westlake Chemical Corporation

Petrothenes

Equistar Chemicals, LP

REXells

Huntsman Corporation

Marlexs

Chevron Phillips Chemical Company LLC

Petromonts

Petromont

Exac ECTFE

Saint Gobain—Norton

Braskem PE

Braskem

RxLOYt

Ferro Corporation

NOTRANs

SK Corporation

HI-ZEXs

Mitsui Chemicals America, Inc.

Formolenes

Formosa Plastics Corporation (Continued )

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

115

Table 6.31 (Continued) Materials

PP

PP copolymer

Trade Names

Suppliers

Lennite

Westlake Plastics Corporation

RxLOYt

Ferro Corporation

Dyneema Puritys

DSM

Stat-Rites

Noveon, Inc.

PRE-ELEC

Premix Thermoplastics, Inc.

Sunoco PP

Sunoco Chemicals, Polymers Division

ADDILENE PMD

ADDIPLAST

Bapolenes

Bamberger Polymers, Inc.

Borealis PP

Borealis A/S

Bormedt

Borealis A/S

Braskem PP

Braskem

CERTENEt

Channel Prime Alliance

CERTENEt

Muehlstein

Daelim Po1ys

Daelim Industrial Co., Ltd.

El-Pros

CCC Chemical Commerce Co., Ltd.

ELTEXs

INEOS Polyolefins

ExxonMobilt PP

ExxonMobil Chemical Company

Global PP

Global Polymers Corp.

HOPELEN

Honam Petrochemical Corporation

INEOS PP

INEOS Polyolefins

M. Holland PP

M. Holland Company

Osterlenes

Osterman & Company

Pro-fax

Basell Polyolefins

Prolens

Polibrasil Resinas S.A.

Sanren

SINOPEC Shanghai Petrochemical Co. Ltd.

TIPPLENs

Tiszai Vegyi Kombinat Rt. (TVK)

Polypropylene PPH

TOTAL PETROCHEMICALS

TITANPRO

Titan Group

WPP PP

Washington Penn Plastic Co. Inc.

YUPLENEs

SK Corporation

Propylux HS

Westlake Plastics Company

Bormedt

Borealis A/S

CABELECs

Cabot Corporation

Polyforts

A. Schulman Inc.

VYLENE

Lavergne Group

Marlexs

Phillips Sumika Polypropylene Company (Continued )

116

PLASTICS

IN

MEDICAL DEVICES

Table 6.31 (Continued) Materials

PP random copolymer

COC PS

Trade Names

Suppliers

ExxonMobilt PP

ExxonMobil Chemical Company

Formolenes

Formosa Plastics Corporation, U.S.A.

Huntsman Polypropylene

Huntsman Corporation

Purell

Basell Polyolefins

CERTENEt

Channel Prime Alliance

Sunoco PP

Sunoco Chemicals, Polymers Division

CERTENEt

Muehlstein

SEETEC PP

SEETEC

TIPPLENs

Tiszai Vegyi Kombinat Rt. (TVK)

Bormedt

Borealis A/S

Borsoftt

Borealis A/S

El-Pros

CCC Chemical Commerce Co., Ltd.

ExxonMobilt

ExxonMobil Chemical Company

Formolenes

Formosa Plastics Corporation, U.S.A.

Halene P

Haldia Petrochemicals Ltd.

Huntsman PP

Huntsman Corporation

INEOS PP

INEOS Polyolefins

Moplen

Basell Polyolefins

Pro-fax

Basell Polyolefins

Purell

Basell Polyolefins

RANPELEN

Honam Petrochemical Corporation

YUPLENEs

SK Corporation

Topas

Topas Advanced Polymers

Zeonor

Zeon

Bayblends

Bayer Materials

Chem PS

Chevron Phillips

Royalite

Spartech Royalite

API PS

American Polymers, Inc.

Austrex

Polystyrene Australia Pty Ltd.

Crystal PS

NOVA Chemicals

Deltech PS

Deltech Polymers Corporation

Edistirs

Polimeri Europa

INEOS PS

INEOS Styrenics

Lacqrenes

TOTAL PETROCHEMICALS

SUPREME

Supreme Petrochem Ltd.

LACQRENE

Arkema

STYRONs

Dow Chemical

VESTYRONs 314

Creanova, Inc. (Continued )

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

117

Table 6.31 (Continued) Materials

HIPS

Trade Names

Suppliers

LG Chemical Styrenics

LarSan Chemical Company

Resirenes

Calsak Corporation

CP Chem PS

Chevron Phillips Chemical Company LLC

INEOS PS

INEOS Styrenics

Lacqrenes

TOTAL PETROCHEMICALS

NOVA Chemicals PS

NOVA Chemicals

SUPREME SH

Supreme Petrochem Ltd.

VPI PS

VPI, LLC

Kumho PS

Kumho Chemicals, Inc.

Promaluxs

Westlake Plastics

Propyluxs

Westlake Plastics

labware for diagnosis and analysis and medical packaging. High impact polystyrenes is used in medical parts and components and applications (like bottles and containers) where impact resistance is more important. Table 6.30 details some of the applications and requirements for polystyrenes.

6.7 Conclusion Commodity thermoplastics comprise over 70% of all plastics used for medical device applications. Their cost to performance ratio is unbeatable especially for disposable applications. Polyvinyl chloride alone has about a 25% share of the plastics usage. Plasticizers used in PVC formulations especially DEHP-continue to be evaluated for health and toxicity reasons and several DEHP-free alternatives are being offered. Recent advances in the production of high molecular weight, stereospecific polyolefins and stabilization technologies have made them viable options in a wide variety of applications. Cyclo olefin copolymers are a new class of materials offering higher heat, thermal stability and chemical resistance over standard polyolefins. Polystyrene and its derivatives and blends are used in several diagnostic devices and labware applications.

6.8 Commodity Thermoplastics Suppliers Suppliers of commodity thermoplastics are listed in Table 6.31.

References [1] Hong KZ An overview of polyvinyl chloride (PVC) and alternatives in medical applications Proceedings ANTEC 2000 Volume III p. 2704 2709. [2] Patrick S. Rapra Rev Rep 2004;15(3):3 42. [3] Plast Addit Compd; 2004:46 9. September/ October. [4] Vinhas GM, et al. Polym Degrad Stabil 2004;86:431 6. [5] Nielsen Medical Plastics Proceedings; 2006. [6] European Pharmacopoeia, Part 1I 2, 2nd ed. 1981 (Section VI 1.2. Plastic materials and 2.2. Plastic containers). [7] Cadogan DF, ECPI, Brussels, Belgium. Addcon 2002. In: The International Plastics Additives and Modifiers Conference, eighth, Budapest, Hungary, October 22 23, 2002, Plasticizers for PVC: Health and Environmental Impact; 2002. p. 33 43. [8] Fanelli R, Zuccato E. Risks and benefits of PVC in medical applications. Boll Chim Farm 2002;141(4):282 9. [9] Joel AT, Ted S, Tee G, Michael M, Mark R. Health risks posed by use of di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review. Am J Indus Med 2001;39 (1):100 11. [10] MDDI. THERMOPLASTICS: Polyurethane Film as an Alternative to PVC and Latex MATERIAL CHOICES, located on Medical Device Link at, ,http://www.devicelink.com/

118

[11] [12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20] [21]

PLASTICS

mddi/archive/02/09/004a.html.; [accessed September 2002]. Dennis J. J Pharmaceut Sci 2007;96(10): 2566 81. Heudorf U, Mersch-Sundermann V, Angerer E. Phthalates: toxicology and exposure. Int J Hyg Environ Health 2007;210(5):623 34. Health Canada Expert Advisory Panel on DEHP in Medical Devices: Final Report January 11, 2002, ,http://www.hc-sc.gc.ca/ hpb-dgps/therapeut/zfiles/english/advcomm/ eap/dehp/eap-dehp-final-report-2002-jan-11_ e.pdf.. Safety Assessment of Di(2-ethylhexyl)phthalate (DEHP) Released from PVC Medical Devices, Center for Devices and Radiological Health, U.S. Food and Drug Administration, ,http://www.fda.gov/cdrh/ost/dehp-pvc.pdf.; (undated). European Commission, Health & Consumer Protection Directorate-General of The European Commission, Opinion on Medical Devices Containing DEHP Plasticised PVC; Neonates and Other Groups Possibly at Risk from DEHP Toxicity, Document: SANCO/ SCMPMD/2002/0010 Final, ,http://europa. eu.int/comm/food/fs/sc/scmp/out43_en.pdf.; [accessed 26.09.02]. Medical Devices Made With Polyvinyl chloride (PVC) Using the Plasticizer di-(2Ethylhexyl)phthalate (DEHP); Draft Guidance for Industry and FDA, ,http://www.fda.gov/ [accessed cdrh/ode/guidance/1407.pdf.; 06.09.02]. Frequently Asked Questions Regarding PVC and DEHP in Medical Devices, HIMA, ,http://www.advamed.org/publicdocs/faq499. pdf.; [accessed 00.04.02]. EUCOMED Position on the Use of Phthalate Plasticized PVC in Medical Products. ,http:// www.medicalplast.com/upload/documents/ document4.pdf.; [accessed 12.12.00]. Hansen CM. On predicting environmental stress cracking in polymers. Polym Degrad Stabil 2002;77:43 53. Zahran AH, Hegazy EA, Ezz Eldin FM. Radiat Phys Chem E 1984;32:25 6. Begazy EA, Seguchi T, Machi S. Radiation induced oxidative degradation of polyvinylchloride. J Appl Polym Sci 1981;26:2947.

IN

MEDICAL DEVICES

[22] Clough RL, Gillen KT. Complex radiation degradation behavior of PVC material. Radiat Phys Chem 1983;22:527. [23] Clough RL, Gillen KT. Radiation-thermal degradation of PE and PVC: mechanism of synergism and dose rate effects. Radiat Phys Chem 1981;18:661. [24] Baccaro S, et al. Nucl Instrum Methods Phys Res B 2003;208:195 8. [25] Chapiro A. Action des rayons gamma sur les polymers a l’e´tat solide, III Irradiation du chlorure de polyvinyle. J Chim Phys 1956;53:895. [26] Vinhas GM, Souto Maior RM, de Almeida YMB. Polym Degrad Stabil 2004;83:429 33. [27] Vinhas GM, Souto Maior RM, de Almeida YMB, Netto BB. Polym Degrad Stabil 2004;86:431 6. [28] Luther DW, Linsky LA. Improving gamma radiation resistance: medical grade, flexible PVC compounds. J Vinyl Addit Technol 1996;2(3). [29] Wang QI, Nagy S. Improving gammaradiation stability of PVC a review. J Vinyl Addit Technol 1999;5(1):4 11. [30] Brunella V. PVC Stabilization during sterilization with electron beam. In: Proceedings of the Medical Polymers; 2003. p. 159 166. [31] McShane P, Mayoral B, McLaughlin D. In: Proceedings of the SPE ANTEC; 2005. p. 3071 4. [32] Zhao XB, Courtney JM. Blood response to plasticized polyvinyl chloride. Dependence of fibrinogen adsorption on plasticizer selection and surface plasticizer level. J Mater Sci Mater Med 2003;14(10):905 1012. [33] Zhao XB, Courtney JM. Influence on blood of plasticized polyvinyl chloride: significance of the plasticizer Bioengineering Unit, University of Strathclyde, Glasgow, United Kingdom Artif Organs 1999;23(1):104 7. [34] Faouzi MA, et al. Int J Pharmaceut 1999;180: 113 21. [35] Hanawa T, et al. Int J Pharmaceut 2000;210: 109 15. [36] Kambia R, et al. Int J Pharmaceut 2001;229: 139 46. [37] Jaeger RJ, Robert JR. Nutrition 1997;13(11): 1011 2. [38] Lappegard KT, et al. Ann Thorac Surg 2005;79:917 23.

6: COMMODITY THERMOPLASTICS: POLYVINYL CHLORIDE, POLYOLEFINS, AND POLYSTYRENE

[39] Van Tienhoven EAE, et al. J Biomed Res A 2006;175 82. [40] Kulshreshtha AK. Polym Plast Technol Eng 1993; 32(6):551 78, 1525 6111. [41] McConnell D, McNally GM, Murphy WR. In: Proceedings of the 2004 Medical polymers, Dublin, Ireland, November 2004. p. 125 42. [42] Chandan KG. In: Proceedings of the Plastics in healthcare, SPE, February 2002. p. 30 2. [43] Karol FJ, Jacobson FI. Catalytic polymerization of olefins. In: Proceedings on future aspects of olefin polymerization, Tokyo, Japan; 1985. p. 323 38. [44] Kaminsky W, Laban A. Appl Catal A 2001;222:47 61. [45] Kaminsky W. Chemosphere 2001;43:33 8. [46] Brubeck RA. Mater Sci Eng 2002;R39:1 28. [47] Rau A, Schmitz S, Luft G. Chem Eng Technol 2002;25(5):494 8. [48] Sinn H, Kaminsky W, Vollmer HJ, Woldt R. Angew Chem 1980;92:396. [49] Lustiger A. In: Portnoy RC, editor. Medical plastics degradation and failure analysis; 1998. p. 65 72. [50] Navarette L, Hermanson N. In: Proceedings of the SPE ANTEC; 1996. p. 2807 18. [51] Costa L, Bracco P. Mechanism of cross linking and oxidative degradation of UHMWPE. In: Kurtz S, editor. The UHMWPE handbook: ultra-high molecular weight polyethylene in total joint replacement. Academic Press; 2004, p. 235 61. Chapter 11. [52] Jahan MS, McKinney KS. Nucl Instrum Methods Phys Res B 1999;151:207 12. [53] Mallegol D, Carlsson DJ, Deschenes L. Nucl Methods Instrum Phys Res B 2001;85:283 93. [54] Suarez JCM, De Biasi RS. Polym Degrad Stabil 2003;11(82):221 7. [55] Affatato S, et al. Tribol Int 2008;41:813 22. [56] Affatato S, et al. Biomaterials 2003;24: 4045 55. [57] Shang S, et al. J Vinyl Addit Technol 1998;4(1):60 4. [58] Oral E, et al. Biomaterials 2005;26(6): 657 66. [59] Malle´gol J, Carlsson DJ, Descheˆnes S. J Polym Degrad Stabil 2001;73:269. [60] Taddei P, Affatato S, Rocchi M, Fagnano C, Viceconti M. J Mol Struct 2008;875:254 63. [61] Liao YS, McNulty D, Hanes M. Wear 2003;255:1051 6.

119

[62] Santavirta S, et al. Clin Orthop Rel Res 1993;297:100 10. [63] Marie-Claire B, Yves Marois J. Biomed Mater Res B Appl Biomater 2001;58(5):467 77. [64] Reno F, Lombardi F, Cannas M. Biomaterials 2003;24:2895 900. [65] Takami Y, Nakazawa T, Makinouchi K, et al. J Biomed Mater Res 1997;36(3):381 6. [66] Cosmetic Ingredient Review Expert Panel. Int J Toxicol 2007;26(Suppl. 1):115 27. [67] Kazuo S, Takeshi S. Ziegler Natta catalysts for olefin polymerizations. Prog Polym Sci 1997;22(7):1503 46. [68] Galli P, Vecellio G. Prog Polym Sci 2001;26: 1287 336. [69] De Rosa C, Auriemma F. Prog Polym Sci 2006;31:145 237. [70] Kaminsky W. J Chem Soc Dalton Trans 1998;1413 8. [71] Kaminsky W. Pure Appl Chem 1998;70(6): 1229 33. [72] Libster D, Aserin A, Garti N. Polym Adv Technol 2007;18:685 95. [73] Albano C, Perera C, Karam A, et al. Beam interactions with materials and atoms. Nucl Instrum Methods Phys Res B 2007;265(1): 265 70. [74] Yagoubi N, Boucherie P, Ferrier D. Nucl Instrum Methods Phys Res B 1997;131: 398 404. [75] Alariqi SAS, et al. Polym Degrad Stabil 2007;92(2):99 309. [76] Aymes-Chodur C. Polym Degrad Stabil 2006;91:649 62. [77] Ahmad S. Polym Additives Compound 2005;38 45. [78] Matthijs. Medical polymers; 2004. [79] Shamshad A, Basfar AA. Radiat Phys Chem 2000;57:447 50. [80] Elvidio de Paula ES, Everton LSR, Se´rgio VB. Braz Dent J 2001;12(2):121 5. [81] Scheidbach H, et al. Surg Endosc 2004;18: 211 20. [82] Jones JW, Jurkovich GJ. Polypropylene mesh closure of infected abdominal wounds. Am Surg 1989;55:73 6. [83] Van Der Velden MA, Klein WR. A modified technique for implantation of polypropylene mesh for the repair of external abdominal hernias in horses: a review of 21 cases. Vet Quart 1994;16:108 10.

120

[84] Anderson AW, Merckling NG. U.S. Patent 2 (721) (1955) 189. [85] Anderson AW, Merckling NG. Chem Abstr 1955;50:3008. [86] Dragutan V, Balban AT, Dimonie M. Olefin metathesis and ring-opening polymerization of cyclo-olefins. New York: Wiley; 1985.

PLASTICS

IN

MEDICAL DEVICES

[87] Pariya C, Jayaprakash KN, Sarkar A. Coord Chem Rev 1998;168:1 48. [88] Nielsen TB, Hansen CM. Polym Degrad Stabil 2005;89(3):513 6. [89] Hermanson NJ, Navarette L, Crittenden P. Medical device and diagnostic industry, August 1997.