**6.2 Action of stabilizers in polymeric medical device exposed to gamma sterilization**

With the development of space science, the stability of polymeric materials against radiation has been drawing the attention of scientists. Polymers which contain aromatic groups are well known to have relatively good radiation stability, but are also very expensive. The practical solution of these protection tasks are connected to specific chemical agents, well engineered polymer additives, elaborated mainly for the stabilization of general purpose polymers. The radiation stabilizers, called "antirads" represent only a modest, but flourishing fraction of that thermo-oxidative- and UV stabilizers.

The reason behind the parallel technical development of conventional and radiation stabilizers is related to the fact, that the UV degradation and thermo-oxidative degradation as well as radiation degradation of polymers are all similar chain reactions. As such, these processes consist of several steps of: chain initiation, chain propagation, chain branching and chain termination. The scheme according to which these reactions proceed on a H containing polymer chain P is seen in Figure 6. In spite of the differences in fine details the task is similar in all the three main (thermooxidative, UV and radiation) degradation processes, namely to control and/or diminish the danger of deterioration of properties either by preventing chain initiation, and/or stopping chain propagation.

Additives may promote radiolytic stabilization on properties of polymers thought two primary mechanisms: a) scavenging of excited-state energy (quenching), and b) scavenging of paramagnetic species (free radicals, secondary electrons). Also the incorporation of additives, plasticizing type, act as "mobilizer" on polymer chains. Additives and stabilizers

Sterilization by Gamma Irradiation 197

Table 7. Some commercial additives used in the stabilization of polymer gamma sterilized

radiolytic stabilization of polymers has been published. The efficiency of a certain additive in the stabilization of polymer molecules against radiation may be evaluated by measuring the effect of this additive on the free radical population after irradiation, as well as on its rate of decay. The efficiency of HALS additives depends on their molecular weight, structure, solubility and concentration in the polymer matrix. Conversion of amines into nitroxyl radicals following the reaction with peroxyl radicals leads to relatively stable intermediate species. Regeneration of the nitroxyl radical limits the consumption of HALS

**Structure Comercial** 

**name** 

Irganox 1010 primary

Irganox 168 secondary

<sup>800</sup>secondary

Tinuvin 622 secondary

Irganox PS

**Classification of antioxidant** 

are commonly included in small amounts (less than 1%) in commercial polymer products to aid in processing, stabilize the material and impart particular properties to the product. In controlling the route of those oxidative chain reactions, there are two main types of antioxidant stabilizers:


Typical primary antioxidants, interfering with the chain-carrying radicals are the orthodisubstituted phenols, alkylphenols, hydroxyphenyl propionates and hydroxybenzyl compounds. Irganox 1010 (see structure in Table 7) is one of the most important additive protecting PE and PP in radiation sterilization. It is important to note, that such stabilizers are never used alone. Secondary antioxidants represent an even greater group of sophisticated organic molecules: aromatic amines, organic sulfur compounds (typically thiobisphenols and thioethers) as well as phosfites and sterically hindered amines. These two latter type of compounds are successfully applied in the radiation-stabilization of PP (Williams et al., 1977). The Table 7 showed some commercial antioxidant structures.

Clearly, the radiation-protection stabilizer systems should fulfill a whole series of other requirements such as chemical, physical and toxicological safety. Take for example the blood-taking and transfusion sets, made out of plasticized PVC, radiation sterilized and then stored (standing by) for years, later filled with chemically stabilized blood, and cooled and stored again. During all these procedures the protected polymeric material should be stable, should not loose its elasticity, and in the last steps there are strict limitations on traces of all chemicals extractable by the blood.

In relation to radiation stability improvement, discoloration of PP homopolymer was eliminated by the incorporation of the light protector in the samples prepared by injection moulding. Samples of PP homopolymer with different additives also were prepared by compression moulding were irradiated to 25 kGy. The commercial additives used were Tinuvin 622, Irganox B225 (blend of Irganox 1010 and Irganox 168), Irganox PS800 and Irganox 1010. The structures of these commercial additives were showed in Table 7. Elongation to break was measured after irradiation and at 12 months of aging at room temperature. Previous experiments with samples prepared in the same way without additives had shown a strong effect of post irradiation degradation and this effect could be anticipated by the effect of a higher applied dose. The effect of additives was significant as all of additived samples could be considered functional after aging. Addition of antioxidants improved mechanical stability in samples prepared by compression molding and by injection moulding, but they had a negative effect in discoloration (Gonzales & Docters, 1999)

Hindered Amine Light Stabilizer (HALS) is among the more extensively used additives for protecting polymers against degradation by the combined effect of light, temperature, and atmospheric oxygen. The protection of the polymer from the light by these compounds takes place via a mechanism involving photo-oxidation of the amines to nitroxyl radicals (Lucarini et al, 1996). Nitroxyl radical is capable of scavenging the radicals through a reaction called Denison cycle. On the other hand, very little information on this additive for

are commonly included in small amounts (less than 1%) in commercial polymer products to aid in processing, stabilize the material and impart particular properties to the product. In controlling the route of those oxidative chain reactions, there are two main types of

Primary or chain-breaking antioxidants interfere with the chain propagation step. That

Secondary or preventive antioxidants destroy hydro-peroxide groups, responsible for

Typical primary antioxidants, interfering with the chain-carrying radicals are the orthodisubstituted phenols, alkylphenols, hydroxyphenyl propionates and hydroxybenzyl compounds. Irganox 1010 (see structure in Table 7) is one of the most important additive protecting PE and PP in radiation sterilization. It is important to note, that such stabilizers are never used alone. Secondary antioxidants represent an even greater group of sophisticated organic molecules: aromatic amines, organic sulfur compounds (typically thiobisphenols and thioethers) as well as phosfites and sterically hindered amines. These two latter type of compounds are successfully applied in the radiation-stabilization of PP

(Williams et al., 1977). The Table 7 showed some commercial antioxidant structures.

Clearly, the radiation-protection stabilizer systems should fulfill a whole series of other requirements such as chemical, physical and toxicological safety. Take for example the blood-taking and transfusion sets, made out of plasticized PVC, radiation sterilized and then stored (standing by) for years, later filled with chemically stabilized blood, and cooled and stored again. During all these procedures the protected polymeric material should be stable, should not loose its elasticity, and in the last steps there are strict limitations on traces

In relation to radiation stability improvement, discoloration of PP homopolymer was eliminated by the incorporation of the light protector in the samples prepared by injection moulding. Samples of PP homopolymer with different additives also were prepared by compression moulding were irradiated to 25 kGy. The commercial additives used were Tinuvin 622, Irganox B225 (blend of Irganox 1010 and Irganox 168), Irganox PS800 and Irganox 1010. The structures of these commercial additives were showed in Table 7. Elongation to break was measured after irradiation and at 12 months of aging at room temperature. Previous experiments with samples prepared in the same way without additives had shown a strong effect of post irradiation degradation and this effect could be anticipated by the effect of a higher applied dose. The effect of additives was significant as all of additived samples could be considered functional after aging. Addition of antioxidants improved mechanical stability in samples prepared by compression molding and by injection moulding, but they had a negative effect in discoloration (Gonzales & Docters,

Hindered Amine Light Stabilizer (HALS) is among the more extensively used additives for protecting polymers against degradation by the combined effect of light, temperature, and atmospheric oxygen. The protection of the polymer from the light by these compounds takes place via a mechanism involving photo-oxidation of the amines to nitroxyl radicals (Lucarini et al, 1996). Nitroxyl radical is capable of scavenging the radicals through a reaction called Denison cycle. On the other hand, very little information on this additive for

step is the main carrier of the oxidative degradation.

chain initiation and chain branching.

of all chemicals extractable by the blood.

1999)

antioxidant stabilizers:


Table 7. Some commercial additives used in the stabilization of polymer gamma sterilized

radiolytic stabilization of polymers has been published. The efficiency of a certain additive in the stabilization of polymer molecules against radiation may be evaluated by measuring the effect of this additive on the free radical population after irradiation, as well as on its rate of decay. The efficiency of HALS additives depends on their molecular weight, structure, solubility and concentration in the polymer matrix. Conversion of amines into nitroxyl radicals following the reaction with peroxyl radicals leads to relatively stable intermediate species. Regeneration of the nitroxyl radical limits the consumption of HALS

Sterilization by Gamma Irradiation 199

way is to directly inhibit the formation of A radical by quencher mechanism when Tinuvin 622 may be to absorb the energy of the excited molecules in PMMA via an intermolecular energy transfer and possibly convert the absorbed energy. The other way is based on ESR results, the A radical to be scavenged by a nitroxyl radical and an alkyloxyamine is formed. The alkyloxyamine scavenges a peroxyl radical in a second step, in which the nitroxyl

Vinhas et al. (2004) also reported radio-protective action of a common photo-oxidative stabilizer, HALS, in PVC films plasticized with DEHP (di-2-ethylhexyl phthalate). The HALS additive is believed to interrupt oxidative propagation reaction by scavenging of

On the other hand polymer blends are an attractive route to formation of a novel material. Polystyrene, PS, contains aromatic groups that increase radiation resistance and stabilizes the excited species formed by irradiation. The presence of PS in PVC/PS blends could be an interesting route to PVC radiolytic stabilization. The analysis of Figure 14 revealed that at 0- 15 kGy the main effect of gamma irradiation on PVC is crossllinking and at 25-100 kGy the main chain effect is predominant. However, the PS in the blend system inhibits crosslinking in the lower irradiation dose range (0–15 kGy) and less chain scission occurs in PVC/PS film than in PVC film. At a sterilization dose (25 kGy) were found a decrease of 65% (95/05) and 47% (90/10) in scissions per original molecule of PVC (Silva et al, 2008). The PS molecule acts as an additive and the aromatic groups of PS structure absorb the excitation energy and a lower bond cleavage yield is noted. This in turn causes a decrease in the formation of free radicals, which are responsible for scission degradation reaction. The mechanisms of main

Fig. 14. Reciprocal of Mv as a function of the irradiation dose of PVC and PVC/PS blends

radical is regenerated (Aquino & Araujo, 2008).

scission and crosslinking of PVC have been showed in Figure 7.

chlorine radical formed in PVC radiolysis.

during degradation allowing the use of these additives in low concentration. Tinuvin 622 (see structure in Table 7) is a macromolecular HALS, which exhibits a quite high thermal stability. This additive starts to decompose around 4000C with intramolecular ester group rearrangement. Final decomposition events occur at 9000C and include nitrile and hydrogen cyanide formation (Lucarini et al., 1996)

Samples of PMMA irradiated at 30 kGy and containing Tinuvin 622 showed more resistance to radiation damage. Tinuvin 622 also induces a faster evolution of radicals produced on PMMA radiolysis, which can result in the inhibition of free radical damage. Above 30 kGy, both PMMA without (PMMA-control) PMMA with Tinuvin 622 (PMMA-622) undergo significant changes in the yellowness index with increase of absorbed dose due to conjugated center that absorbs light in the visible range. After 63 days of storage at 30 kGy dose, the yellowness index measured was 2.78 and 0.17 to PMMA-control and PMMA-622, respectively. These results showed that the Tinuvin 622 is a good alternative for stabilizing the PMMA against gamma irradiation damage in sterilization processes with low cost (Aquino et al., 2010)

The scheme in Figure 13 is generally accepted to explain the aspects of the chemistry mechanism of HALS action to inhibit polymer photo-oxidation. This scheme was used to guide a strategy to assess Tinuvin 622 action in radiolytic stabilization of PMMA (Aquino & Araujo, 2008). According to this scheme, the tetramethylpiperidine moiety, which is the basic structure of HALS, is initially oxidized to produce a nitroxyl radical by gamma irradiation. The nitroxyl radical acts as a scavenger of the radical originating from the irradiation of polymer chain substrate to form an alkylated aminoether. From the aminoether, the nitroxyl radical is regenerated through quenching another peroxyradical produced by oxidation of the polymer chain. Thus the nitroxyl radicals could regenerate many times through the chain reaction before their depletion.

Fig. 13. Typical photo-stabilizing action of HALS in the polymer system

The single Electron Spin Resonance (ESR) spectrum was obtained for Tinuvin 622 sample irradiated at 100 kGy and was attributed to nitroxyl radical (Aquino et al., 2010). The chemistry of HALS had been widely documented for UV irradiation. As the Tinuvin 622 is a tertiary HALS a sequence of reactions starting with amine ionization and a-aminoalkyl radicals are formed. These radicals rapidly react with oxygen and fragment under the elimination of formaldehyde to nitroxyl radicals. Thus, similar stabilization mechanism is attributed to Tinuvin 622 when the PMMA is submitted to gamma irradiation. The gamma rays can break covalent bonds in PMMA molecule to directly produce the free radicals as was shown in Figure 8 (II). The gamma rays can also produce excited states in PMMA which undergo further reactions to produce the A radical (Figure 8) indirectly. Thus, there are two ways for Tinuvin 622 to decrease the main scission effect of gamma-irradiated PMMA. One

during degradation allowing the use of these additives in low concentration. Tinuvin 622 (see structure in Table 7) is a macromolecular HALS, which exhibits a quite high thermal stability. This additive starts to decompose around 4000C with intramolecular ester group rearrangement. Final decomposition events occur at 9000C and include nitrile and hydrogen

Samples of PMMA irradiated at 30 kGy and containing Tinuvin 622 showed more resistance to radiation damage. Tinuvin 622 also induces a faster evolution of radicals produced on PMMA radiolysis, which can result in the inhibition of free radical damage. Above 30 kGy, both PMMA without (PMMA-control) PMMA with Tinuvin 622 (PMMA-622) undergo significant changes in the yellowness index with increase of absorbed dose due to conjugated center that absorbs light in the visible range. After 63 days of storage at 30 kGy dose, the yellowness index measured was 2.78 and 0.17 to PMMA-control and PMMA-622, respectively. These results showed that the Tinuvin 622 is a good alternative for stabilizing the PMMA against gamma irradiation damage in sterilization processes with low cost

The scheme in Figure 13 is generally accepted to explain the aspects of the chemistry mechanism of HALS action to inhibit polymer photo-oxidation. This scheme was used to guide a strategy to assess Tinuvin 622 action in radiolytic stabilization of PMMA (Aquino & Araujo, 2008). According to this scheme, the tetramethylpiperidine moiety, which is the basic structure of HALS, is initially oxidized to produce a nitroxyl radical by gamma irradiation. The nitroxyl radical acts as a scavenger of the radical originating from the irradiation of polymer chain substrate to form an alkylated aminoether. From the aminoether, the nitroxyl radical is regenerated through quenching another peroxyradical produced by oxidation of the polymer chain. Thus the nitroxyl radicals could regenerate

The single Electron Spin Resonance (ESR) spectrum was obtained for Tinuvin 622 sample irradiated at 100 kGy and was attributed to nitroxyl radical (Aquino et al., 2010). The chemistry of HALS had been widely documented for UV irradiation. As the Tinuvin 622 is a tertiary HALS a sequence of reactions starting with amine ionization and a-aminoalkyl radicals are formed. These radicals rapidly react with oxygen and fragment under the elimination of formaldehyde to nitroxyl radicals. Thus, similar stabilization mechanism is attributed to Tinuvin 622 when the PMMA is submitted to gamma irradiation. The gamma rays can break covalent bonds in PMMA molecule to directly produce the free radicals as was shown in Figure 8 (II). The gamma rays can also produce excited states in PMMA which undergo further reactions to produce the A radical (Figure 8) indirectly. Thus, there are two ways for Tinuvin 622 to decrease the main scission effect of gamma-irradiated PMMA. One

many times through the chain reaction before their depletion.

Fig. 13. Typical photo-stabilizing action of HALS in the polymer system

cyanide formation (Lucarini et al., 1996)

(Aquino et al., 2010)

way is to directly inhibit the formation of A radical by quencher mechanism when Tinuvin 622 may be to absorb the energy of the excited molecules in PMMA via an intermolecular energy transfer and possibly convert the absorbed energy. The other way is based on ESR results, the A radical to be scavenged by a nitroxyl radical and an alkyloxyamine is formed. The alkyloxyamine scavenges a peroxyl radical in a second step, in which the nitroxyl radical is regenerated (Aquino & Araujo, 2008).

Vinhas et al. (2004) also reported radio-protective action of a common photo-oxidative stabilizer, HALS, in PVC films plasticized with DEHP (di-2-ethylhexyl phthalate). The HALS additive is believed to interrupt oxidative propagation reaction by scavenging of chlorine radical formed in PVC radiolysis.

On the other hand polymer blends are an attractive route to formation of a novel material. Polystyrene, PS, contains aromatic groups that increase radiation resistance and stabilizes the excited species formed by irradiation. The presence of PS in PVC/PS blends could be an interesting route to PVC radiolytic stabilization. The analysis of Figure 14 revealed that at 0- 15 kGy the main effect of gamma irradiation on PVC is crossllinking and at 25-100 kGy the main chain effect is predominant. However, the PS in the blend system inhibits crosslinking in the lower irradiation dose range (0–15 kGy) and less chain scission occurs in PVC/PS film than in PVC film. At a sterilization dose (25 kGy) were found a decrease of 65% (95/05) and 47% (90/10) in scissions per original molecule of PVC (Silva et al, 2008). The PS molecule acts as an additive and the aromatic groups of PS structure absorb the excitation energy and a lower bond cleavage yield is noted. This in turn causes a decrease in the formation of free radicals, which are responsible for scission degradation reaction. The mechanisms of main scission and crosslinking of PVC have been showed in Figure 7.

Fig. 14. Reciprocal of Mv as a function of the irradiation dose of PVC and PVC/PS blends

Sterilization by Gamma Irradiation 201

irradiation as an alternative treatment to pesticides for fruits and vegetables that are considered hosts to a number of insect pests including fruit flies and seed weevils. The irradiation produces no greater nutrient loss than what occurs in other processing methods. However, the irradiation reduces the vitamin content of food, the effect of which may be indirect in that inadequate amounts of antioxidant vitamins (such as C, E, and β-carotene) may be available to counteract the effects of free radicals generated by normal cell metabolism. In addition, the most affected lipids during irradiation are thus the

When radiation is used for the sterilization of medical devices, the compatibility of all of the components has to be considered. Ionizing radiation not only kills microorganisms but also affects material properties. When the polymer systems are submitted to sterilization by gamma radiation (25 kGy dose), their molecular structures undergo modification mainly as a result of main chain scission and crosslinking effects. Both processes coexist and either one may be predominant depending not only upon the chemical structure of the polymer, but also upon the conditions like temperature, environment, dose rate, etc., under which

The protection of polymers against sterilization dose requires efficient additives preventing and/or stopping chain reaction type oxidative degradation. Primary and secondary antioxidants work well here in synergy. Polymer blend and nanoparticles also may be used in radiolytic stabilization of polymer used in medical devices. Commercial raw materials are available for radiation-sterilizable medical devices made of polyolefins and other thermoplastics. Similarly, polymer compounds of suitable formulae are offered

Action biologique et chimique des rayonnements ionisants (ABCRI). (2001). B.Tilquin (Ed.),

Al-Kahtani, H. A.;Abu-Tarboush, M. H.; Bajaber, A. S.; Atia, M. ;Abou-Arab, A. A.& El-

Alariqi, S.A.S.; Pratheep, A. K.; Rao, B. S. M. & Singh, R. P. (2006). Biodegradation of γ-

environments. *Polymer Degradation Stability*, Vol. 91, N° 6, pp. 1105–1116. American Society for Testing and Materials. (2006). Standard Guide for Selection and

Annual Book of ASTM Standards, ASTM, p.p 970–988, USA, New York, Aquino, K. A. S. & Araujo, E. S. (2008). Effects of a Hindered Amine Stabilizer (HAS) on

Aquino, K. A. S.; Araujo, E. S & Guedes, S. M. (2010). Influence of a Hindered Amine

Mojaddidi, M. A. (1996). Chemical changes after irradiation and post-irradiation storage in Tilapia and Spanish mackerel. *Journal of Food Science*, Vol. 61, pp. 729-733

sterilised biomedical polyolefins under composting and fungal culture

Calibration of Dosimetry Systems for Radiation Processing, ISO/ASTM 51261,

Radiolytic and Thermal Stability of Poly(methyl methacrylate). *Journal of Applied* 

Stabilizer on optical and mechanical properties of poly (methyl methacrylate) exposed to gamma irradiation. *Journal of Applied Polymer Science*, Vol.116, N° 2, pp.

polyunsaturated fatty acids that bear two or more double bonds.

commercially for high-dose applications in nuclear installations.

*Polymer Science*, Vol. 110, N° 1, pp. 401-401

irradiation is performed.

**8. References** 

748-753

115 pp. Paris, France

In addition, the preparation of polymer films containing disperse nanoparticles has a great interest. The importance of these nanocomposites is due the mechanical, electrical, thermal, optical, electrochemical, catalytic properties that will differ markedly from that of the component materials. For example, the synthesis of Sb2S3 nanoparticles by sonochemical route under ambient air from solution containing antimony chloride as metal source and thioacetamide as a sulfur source produced amorphous powder with monodiperse nanospheres, whose diameters were calculated in the range of 300-500 nm. Films of PVC with Sb2S3 (PVC/Sb) nanoparticles were exposed to gamma irradiation at sterilization dose and the effects of the nanoparticles on the viscosity average molar mass (Mv) of sterilized PVC were studied. The results revealed less chain scissions occur in PVC/Sb films at 0.30 wt% concentration. At sterilization dose (25 kGy) was calculated a decrease of 67% in scissions per original molecule of PVC. No information about use of Sb2S3 in the radiolytic stabilization of polymers has been published and consequently the mechanism of radiolytic stabilization effect of these nanoparticles is not clear. However, some probable reactions may be going on under gamma irradiation.
