Radiation Physics and Chemistry 84 (2013) 223–231

Contents lists available at SciVerse ScienceDirect

Radiation Physics and Chemistry

journal homepage: www.elsevier.com/locate/radphyschem

Effect of electron beam radio sterilization on cyclic olefin copolymers used

as pharmaceutical storage materials
Hala Barakat a,b,n, Caroline Aymes-Chodur a, Johanna Saunier a, Najet Yagoubi a
a
Laboratoire Matériaux et Santé EA 401, IFR 141, Faculté de Pharmacie, Université Paris Sud-11, 5 rue J. B. Clément, 92296 Châtenay-Malabry, France
b
Quality Control Departement, Faculty of Pharmacy, Tishreen University, Latakia, Syria

a r t i c l e i n f o abstract

Article history: The aim of this work was to study the effect of radio-sterilization on cyclo olefin copolymers (COC), that
Received 1 January 2011 can be used as pharmaceutical storage materials, both on the surface and in the volume of the material,
Accepted 1 January 2012 and to investigate the impact of the presence of a lubricant. A cyclo olefin copolymer (TOPASs 8007)
Available online 7 June 2012
was treated with an electron beam radio-sterilization at different doses ranging from 25 to 150 kGy.
Keywords: Polymer structure and bulk properties were evaluated by Fourier Transform Infrared Spectroscopy
COC (FTIR), Differential Scanning Calorimetry (DSC) and Size Exclusion Chromatography (SEC). A good
Electron beam radio-sterilization correlation between those analytical techniques was observed: oxidation products were formed and
Crosslinking crosslinking of chains occured. Although these modifications were important, the effect on the thermal
Low molecular weight compounds
properties was weak. The analysis by Reversed Phase High Performance Liquid Chromatography
Surface modification
(RP-HPLC) of extraction’s solutions of COC after irradiation showed both a remarkable decrease of the
Ageing
extractable amount of polyphenolic antioxidant (Irganox 1010s) initially present in the matrix, and a
generation of an important number of degradation products that represent potential migrants for
pharmaceutical formulations. Surface modifications were evidenced by both (FTIR/ATR) and contact
angle measurements of COC films. An increase in surface polarity of COC after radio-sterilization was
observed.
& 2012 Elsevier Ltd. All rights reserved.

1. Introduction
Cyclic olefin copolymers (COC) belong to a new class of
amorphous polymers having remarkable combination of proper-
ties such as high transparency, low moisture uptake, glass-like
texture, very high heat resistance and good chemical resistance
(Naga et al., 2006; Rische et al., 1998; Yang et al., 2002; Young
et al., 2003). These unique properties make COC interesting for
numerous industrial applications and notably in medical and
pharmaceutical fields (Yamazaki, 2004; Zhang et al., 2008).
Indeed, COC are more and more used as medical devices and
pharmaceutical packaging especially for injectables formulations
(Topass) which require a suitable and reliable sterilization
process.
Electron beam irradiation has been used to sterilize medical
goods for well over 50 years (Abraham et al.; Ansari and Datta,
2003; Fintzou et al., 2007; Haji-Saeid et al.). Because of its
convenience and lower cost, it provides an interesting and prefer-
able alternative sterilization method towards high temperature
n
Corresponding author at: Université Paris Sud-11, IFR 141, Faculté de Phar-
macie, Laboratoire Matériaux et Santé EA 401, 5 rue J. B. Clément, 92296
Châtenay-Malabry, France. Tel.: þ 33 1 46 83 57 74; Fax: þ33 1 46 83 59 63.
E-mail address: hala.barakat@u-psud.fr (H. Barakat).
steam autoclaving or dry heat that can damage materials, induce
degradation and lead to losses of both shape and mechanical
properties.
However, the high-energy electrons released from the inter-
action of electron beam particles with materials are known to
create reactive intermediates and free radicals which follow
several reaction paths and results in crosslinking and/or scission
of the polymer chains (Chapiro, 1988; Clough, 2001; Davenas
et al., 2002). This can modify the mechanical properties as well as
the surface properties of the polymer (Majumder and Bhowmick,
1999). In addition to that, chain scissions cause the production of
low molecular weight compounds (LMWC) (Buchalla and Begley,
2006; Buchalla et al., 1999; El Mansouri et al., 1998), which are
susceptible to migrate from the bulk of polymer onto its surface
and then to the surrounding medium (Bourges et al., 1992a; Lau
and Wong, 2000). Such kind of surface modification and/or
migration of leachables may affect the compatibility of the
couple: content/container, which is an important safety require-
ment in the field of pharmaceutical packaging (Jenke, 2007).
Furthermore degradation process may continue during post-
irradiation shelf-life storage due to the trapped free radicals that
are able to react even when the irradiation has been performed
since a long time (Goldman et al., 1996). It should be noticed that
the degree of the modifications induced by irradiation depends on

0969-806X/$ - see front matter & 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.radphyschem.2012.05.006
224 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231
the structure of the polymer as well as on the conditions of
treatment before, during and after irradiation (irradiation dose,
irradiation atmosphere and the amount of antioxidants added to
the polymer).
The aim of this work was firstly to study the effect of electro-
beam radio-sterilization on cyclic olefin copolymers both in the
bulk and on the surface of the material, then to investigate the
impact of the presence of a lubricant on surface modifications
induced by irradiation, and finally to evaluate post-irradiation
ageing behavior. We focused on the following:
 Modification of polymer chains (oxidation, scission and cross-
linking) that might change the mechanical properties of COC
and generate potential leachables like oligomers.
 Degradation of the antioxidant that could create compounds of
potential toxicity.
 A preliminary study of surface modifications after irradiation
by contact angle measurements, comparison of lubricated and
non-lubricated polymer.
 Effect of accelerated post-irradiation ageing on polymer
oxidation.
A dose of 25 kGy, which is the dose of sterilization recom-
mended by regulatory authorities (Commission of the European
Communities, 1990), was chosen as the lowest dose in our study.
Two other higher doses (75 and 150 kGy) were applied to
emphasize the effect of irradiation.
2. Experimental
2.1. Polymer
We used a cyclo olefin copolymer (COC) called TOPASs 8007
supplied by Ticona (Germany). The polymer is an ethylene and
norbornene based copolymer, it has been used in the form of
granules (|ؼ2 mm), films (thikness¼ 100 mm) or plates
(Fig. 1(a)). We compare the 8007-D61 grade to the 8007- S04
grade (without lubricant), which was partly studied in an other
publication (Saunier et al., 2008). For the 8007-D61 granules, the
surface has been coated with 0.2% of a wax (lubricant) for better
injection molding processing. FTIR, Differential Scanning Calori-
metry (DSC) and Size Exclusion Chromatography (SEC) were
performed on both granules and films. For the analysis of
extractables by HPLC, previous extractions were done on
Fig. 1. (a) Structure of TOPASs 8007 D-61 (b) Structure of Irganox 1010.
granules. In the case of contact angle measurements and post-
sterilization ageing studies, films were used. FTIR Microscopy
analyses were performed on granules and plates.
2.2. Sample irradiation
Samples were irradiated by an electron beam produced by a
high power generator (10 MeV) from a 10 kW power accelerator
(Ionisos, Fr.). Samples were exposed to three different irradiation
doses: 25, 75, and 150 kGy. They were packed under ambient
condition in plastic (small bags) sachets.
2.3. Sample storage
Irradiated samples were stored in the fridge (5 1C) to reduce
the post-sterilization ageing effects. Post-sterilization ageing was
studied by storing some of the samples at 50 1C during several
weeks.
2.4. Size Exclusion Chromatography
SEC analysis was performed at 60 1C in toluene on a PL
laboratory PL-GPC 220 system: three detectors were used: a
refractometer (DRI) (Polymer Laboratories, UK), a 220 R high
temperature differential viscosimeter (DV) (Viscotek, UK and a
PD 2040 high temperature laser light scattering (LS) detector
(Precision Detectors, Inc., USA). Temperature was set at 60 1C. The
solvent flow was of 1 mL/min. The SEC system was controlled by
the PL-GPC 220 Controls software (version 2.01). The data
acquisition and analysis were set by Viscotek softwares (Omnis-
ec—version 4.0).
The polymer concentration was 5 mg/mL. 200 mL was injected
onto two Polymer Laboratories (PL) columns: a 100 Å and a mixed
D whose molecular weights linear range stood respectively up to
4000 g/mol and between 200 and 4  106 g/mol (data given by the
supplier), their granulometry was of 5 mm, their length was of
300 mm and their internal diameter of 7.5 mm.
2.5. Soxhlet extraction
Soxhlet extraction was used to calculate the insoluble ratio of
polymer chains with toluene as a solvent. The soxhlet extraction
duration was of 24 h. Samples and cellulose thimbles were
weighed before and after extraction. The mass of polymer after
extraction corresponds to the insoluble part of the polymer
(crosslinked chains).
2.6. FTIR
The spectrometer apparatus was a Perkin-Elmer Spectrum
2000. It was used in both Attenuated Total Reflection (ATR) mode
with a diamond crystal (Golden Gate-Specac) and in transmission
mode. To express band intensity we used the height of the band.
The wavelength range was set from 4000 to 400 cm  1 with a
resolution of 4 cm  1during 16 scans.
FTIR microscopy analysis (AutoImage FT-IR Microscope
provided by Perkin Elmer) was performed on both lubricated
non-irradiated granules in order to see the lubricant distribution
and non-lubricated irradiated plates to follow the oxidation band
after irradiation. The conditions were the following: The wave-
length range was set from 4000 to 700 cm  1 with a resolution of
8 cm  1 during 8 and 30 scans for granules and plaques respec-
tively. Granules were cut in slides of 60 mm thick with a micro-
tome (Leica RM 2255) and plates were cut to get lumps of
0.95 mm thick. An image map was taken for granules and was
 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231
Table 1
Surface tension and polar component of surface tension for the three liquids used
for contact angle measurement (data from digidrop softwares library).
Liquid Surface tension, Polar component of
sS (mN/m) the surface tension,
sp (mN/m)
Diiodomethane 51.8 0 (0%)
ethylene glycol 48 19 (40%)
of a size 35  35 mm2, while a line profile was realized on plates
with an interval of 20 mm and for 114 points.
2.7. Differential Scanning Calorimetry
DSC analysis was performed on a TA instrument Q1000. The
heating/cooling rate was of 10 C1/min under nitrogen blanketing
(50 mL/min). The temperature ranged was set between 0 and
160 C1. Hermetical aluminum pans (20 mL) were used. For glass-
transition study, only the second temperature raise after a first
heating/cooling cycle was exploited.
2.8. Contact angle measurement
Samples were analyzed during the few days following irradia-
tion and after storage at 50 1C during several weeks. Contact angle
measurements were carried out on films after a liquid drop
deposition, using a contact angle meter (GBX, France) coupled
to the Digidrop Analysis Windropþþ (v1.00.01.01) software. Two
liquids were used: diiodomethane (CH2I2, Merck Schuchardt
OHG), and ethylene glycol (HOCH2CH2OH, E. Merck Darmstadt).
The surface tension (gs) of each solvent as well as its polar (gp)
components are given in Table 1. Ten drops deposited on each
film sample of COC was analyzed.
2.9. Additives extraction
To identify and quantify the additives in the polymer, we used
a dissolution/precipitation process. 3 g of COC granules were
dissolved at reflux in 50 mL of toluene at around 70 1C under
stirring. After complete dissolution, the polymer was precipitated
by slowly adding 50 mL of methanol under stirring. For the
150 kGy irradiated samples, the polymer was only partly soluble.
Polymer was then removed from the extraction solution by
filtration on a paper filter and the precipitate was carefully rinsed
with methanol. Solutions containing additives, oligomers, and
degradation products were then evaporated by use of a rotavapor
at 60 1C (under vacuum). For the SEC experiment, the dry residue
containing extractables was dissolved in 1.5 mL of toluene (HPLC
grade, VWR), while for analysis by HPLC it was dissolved in
a mixture of 1 mL of THF (HPLC grade, VWR) and 1 mL of
acetonitrile (HPLC grade; VWR). Then, the solution was filtered
on a 0.45 mm Teflon filter.
2.10. HPLC
We developed an HPLC method using two mobile solvents
(methanol and water) and an elution gradient. The apparatus
used was constituted of an Ultimate 3000 Dionex assembly with a
gradient pump, an automatic injector and a photodiode Array
detector. The column was a LiChrocarts 250-4 RP-18e (5 mm)
(Lichrosphere, Interchim). The injection volume was of 20 mL and
the flow rate was of 1 mL/ min. Acquisition was done using the
ChromeleonTM software (Dionex).
225
3. Results and discussion
3.1. Effect of electron beam irradiation on the COC bulk
3.1.1. Effect of radiation on polymer degradation
3.1.1.1. FTIR/Transmission. No extensive modification of COC FTIR
spectra was observed after irradiation; only a slight alteration
was observed around 1700 cm  1. In this frequency range, bands
characteristic of CQO functions (1712 cm  1) grew with the
irradiation dose (Fig. 2). It proved that some of the free radicals
in the polymer chains created during irradiation had reacted with
the oxygen of air.
These observations agree with the work of (Šećerov et al.,
(2008); and Kačarević-Popović Zorica et al., (2006) who reported
that the gamma ray-irradiation of TOPASs samples in air gener-
ated free radicals along the chains; these radicals reacted with
molecular oxygen and the peroxy intermediates produced hydro-
peroxy, hydroxyl and ketone functions. Nakade et al. (2010) also
reported the formation of oxidation functions of ethylene–
norbornene copolymers after photo-irradiation and elucidated
the mechanism of formation of photo-degradation products.
3.1.1.2. SEC. SEC analysis was done on the soluble fraction of
polymer, it should be noticed that the polymer was soluble for
25 kGy and 75 kGy doses but the 150 kGy irradiated sample was
only partially soluble. In order to quantify the amount of insoluble
polymer, three different Soxhlet extractions in toluene were done
on 150 kGy irradiated sample. An insoluble ratio of 45% 74%
(n ¼3) was calculated. This ratio corresponds to the ratio of
chemically crosslinked chains in the polymer, and it was in
agreement with chromatogram intensities (Fig. 3) which showed a
decrease of the soluble fraction of polymer with irradiation.
Chromatograms showed also an enlargement of the weight
distribution of the polymer after irradiation that can be
attributed to both scissions and crosslinking of the polymer
chain. Indeed, the polydispersity index Ip increased from 1.2 to
2.4 for the 0 and 150 kGy respectively (Fig. 4(a)). From the
evolution of molecular weights presented in Fig. 4(b)–(d), it
could be noticed that Mn, Mz and Mw began to increase after a
25 kGy dose and the increase of these masses became more
important as the dose increased especially at 150 kGy, so we
can conclude that crosslinking was the predominant phenomenon
and that scission was not significant. Indeed for the 75 and
150 kGy samples, a marked shoulder appeared at an elution
Fig. 2. Zoom on the 1650–1800 cm  1 range of FTIR-transmission spectra of the
non-irradiated sample and the 25, 75 and 150 kGy irradiated TOPASs 8007 D-61
samples.
226 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231
volume of about 9.8 mL, which was characteristic of a new
distribution of higher molecular weight.
These findings were similar to the results obtained by
J. Saunier (Saunier et al., 2008) who showed a predominance of
crosslinking of non-lubricated TOPASs 8007 after electron beam
irradiation.
3.1.1.3. DSC. A calorimetric study was conducted to put into
evidence modifications in the thermal properties. The glass
transition temperature for TOPASs 8007 D-61 was around 81 1C
that is to say a temperature similar to the non-lubricated sample
(Saunier et al., 2008). For the granules, as observed previously
with non-lubricated samples, the differences between irradiated
and non-irradiated samples were slight: a decrease of glass
Fig. 3. SEC chromatogram of TOPASs 8007 D-61 solution for the different
irradiated doses.
Fig. 4. Evolution of polydisperty Index Ip (a) and molecular weight Mn (b) Mz (c) and Mw (d) (n¼ 3).
transition temperature was observed with the irradiation dose
(Fig. 5). This weak decrease (1 1C for 150 kGy sample) could be
explained in part by the increase in chain ends because of
branching (Gibbs and DiMarzio, 1958; Fox and Flory, 1950).
3.1.2. Effect of radiation on the antioxidant degradation
The phenolic antioxidant found in the polymer, after extrac-
tion by a dissolution/precipitation process and analysis of the
extract by HPLC, was Irganox 1010s (Fig. 1(b)). The extracted
amount was about 1550 ppm. As illustrated in Fig. 6, the extrac-
table level of Irganox 1010s had remarkably decreased as the
irradiation dose increased. Similar profile of extractable amount
of antioxidant after irradiation was observed previously (Saunier
et al., 2008) for the non-lubricated polymer. This decrease might
be explained by the degradation of the antioxidant or/and by the
formation of covalent bonds between the degraded molecules and
the polymer chains. Similar kind of bonding had already been
reported (Allen et al., 1991).
Fig. 5. Evolution of the glass transition temperature with irradiation dose for
TOPASs 8007 D-61 (n¼3).
 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231
Fig. 6. Evolution of the extractable amount of Irganox 1010 in TOPASs 8007 D-61
with the irradiation dose (n¼ 5).
Fig. 7. (a) SEC chromatogram of the extract of TOPASs 8007 D-61 after dissolu-
tion/precipitation for the different irradiation doses. (b) Comparaison of polymer
distributions (dissolved polymer and soluble fraction of polymer in the dissolution
precipitation extract) for the non-irradiated samples.
3.1.3. Effect of radiation on the generation of low molecular weight
compounds (LMWC)
LMWC were put into evidence by dissolution/precipitation
extraction of the polymer and analyzing the extract by both SEC
and HPLC. Chromatograms of the extracts corresponding to
irradiated and non-irradiated polymers were compared.
For SEC analysis (Fig. 7 (a)), the chromatogram of the extract
corresponding to the non-irradiated samples revealed the
presence of two major weight distributions, the first one assigned
to the soluble fraction of the polymer after dissolution/precipita-
tion process, this fraction was of lower molecular mass than the
polymer itself (Fig. 7(b)). The second distribution corresponded to
Irganox 1010 s. These two distributions decreased as the irradia-
tion dose increased and new distributions corresponding to both
polymer chain scission and degradation and recombination pro-
ducts of Irganox 1010s appeared.
The study of these LMW molecules, and especially the degra-
dation products of the antioxidant is an important deal because
they are more able to migrate from the polymer into the
pharmaceutical formulation than larger molecules and may
induce toxicity. So to study these potential migrants, we followed
the evolution of extractable degradation products of Irganox
1010s by HPLC analysis because it is a more selective and specific
method than SEC. In the RP-HPLC system used we should remind
that
227
– the smallest retention times correspond to the more polar and
to the smallest molecules.
– as the detector was a diode array one set at wavelengths
between 150 and 500 nm, all degradation products containing
chromophores absorbing in this range could be detected.
On the HPLC chromatogram of the extract corresponding
to the non-irradiated sample (Fig. 8(a) and (b)), there was a
major peak representing Irganox 1010s and many other little
peaks corresponding to both synthesis residues of Irganox
1010s and some of its degradation products that might result
from a postageing process promoted by the extraction process:
during extraction, polymer was heated at 60–70 1C in organic
solvent during about 45 min. After irradiation, some of these
peaks decreased with irradiation dose, and many new
chromatographic peaks appeared. Others increased and some of
them increased up till 25 kGy and then decreased for the higher
doses.
For a 25 kGy dose, a few new peaks were detected at short
retention times (tr) (tr o 11 min or zone A) so they were
characteristic of small molecules. A large number of other peaks
corresponding to larger degradation products were detected in
zone B (tr 411 min) even at retention time greater than that of
Irganox 1010s. A significant decrease of the latter degradation
products (zone B) was observed after irradiation at 75 kGy, on the
contrary the intensity of the peaks located at shorter retention
times (zone A) increased. This might be due to a further degrada-
tion of the longer degradation molecules by cleavage to form
smaller degradation products. Indeed, zone A degradation
products had a maximum of absorbance at wavelength 250 nm
characteristic of carbonyl group (Fig. 8(b)), while the maximum
absorbance for degradation products of zone B was at 280 nm
characteristic of phenolic group (Fig. 8(a)).
For the 150 kGy dose, the intensity of a majority of degrada-
tion products decreased and so it let the intensity of some
degradation products which are smaller than them increase,
while certain peaks had almost disappeared.
These results were identical of those obtained with
non-lubricated polymers that were previously studied, in other
words: there is no impact of the presence of a lubricant on the
degradation products generated after irradiation.
From this study we can conclude that the sterilization dose
25 kGy generated a great number of extractable degradation
products of Irganox 1010 s that means an important number of
potential migrants; these products might be further degraded by
increasing the irradiation dose.
It should be noticed that degradation products of irganox 1010
s
had been already studied in the literature (Allen et al., 1994,
1991; Bourges et al., 1992b). Allen detected more than 50
different compounds in a 50 kGy electron beam irradiated poly-
propylene sample, but most of them were of very low concentra-
tion and thus they could not be identified by mass spectroscopy.
Bourges was able to identify four main degradation products
after irradiation: a phenol, a quinone, a quinone methide and a
hydroxylbenzaldehyde.
In our study, the identification of degradation products of
Irganox 1010 s by HPLC coupled to mass spectroscopy and the
diffusion of these potential migrants into the pharmaceutical
formulation will be discussed in further paper.
As a conclusion on the bulk results, we have evidenced a
predominant crosslinking as well as the formation of oxidation
and degradation products. In the case of a pharmaceutical
formulation which is in contact with the surface of such material,
it is also important to evaluate the surface modification induced
by electron beam irradiation.
228 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231

Fig. 8. HPLC chromatograms of TOPASs 8007 D-61 extractables for non-irradiated sample and 25, 75 and 150 kGy irradiated samples. The detection was performed by
a diode array set at wavelengths (a) 280 nm and (b) 250 nm.

3.2. Effect of electron beam irradiation on the surface

3.2.1. FTIR
In order to understand the effect of lubricant on the modifica-
tion of the irradiated polymer surface, the distribution of lubri-
cant in polymer surface and bulk was studied. The ATR spectra of
non-irradiated polymer showed absorbance bands at 3300, 1637
and 1564 cm  1 for the lubricated polymer (Fig. 9); these absor-
bance bands were characteristic of the presence of lubricant
containing amide functions. The intensity of these bands was
very important for polymer granules and very low for films.
Indeed in the films, the adsorbance bands corresponding to the
lubricant were shifted as compared with granules and were
broader and of lower intensity. The analysis by FTIR micro-
scopy/transmission of a 60 mm section of lubricated granules
showed that there was no lubricant inside. This can be explained
by the fact that granules were only coated with the lubricant and Fig. 9. FTIR/ATR spectra of the non-irradiated lubricated and non-lubricated
TOPASs 8007 Samples (granules and films).
that the films were obtained by melting these coated granules.
As observed in transmission, the ATR spectra of TOPAS 8007
D-61 showed the appearance of an absorbance band at 1712 cm  1 This gradient could be explained by the kinetic of oxygen
characteristic of a new CQO function, whose intensity increased diffusion from surface into volume and must be confirmed by
with irradiation dose. In order to know if the effect of irradiation Electron Spin Resonance (ESR) analysis.
was homogenous on the surface and in the bulk of the polymer,
the band of oxidation observed after irradiation was followed by
microscopy in transmission mode. For the 150 kGy irradiated 3.2.2. Contact angle measurements
samples, a gradient of oxidation from the surface towards Contact angle measurements on the COC surfaces were mea-
the bulk was observed, it was about 300 mm depth (Fig. 10). sured on films before and after treatment by accelerated
 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231
Fig. 10. Profile line of CQO band as compared with a 3405 cm  1 band of polymer from Microscopy FTIR/Transmission for 150 kGy irradiated plates. 3405 cm  1 band
represents a harmonic band or a combinated band of COC which was the same before and after irradiation.
Fig. 11. Evolution of contact angle of TOPASs 8007 (with and without lubricant)
with two solvents for different irradiated doses.
electrons. The contact angles for the virgin untreated COC surface
were about 40 731 and 68 721 for diiodomethane and ethylene
glycol respectively, this result evidenced the apolar nature of COC
because the contact angle increased as the polarity of solvent
increased.
No significant difference was observed between both kinds of
COC (with and without lubricant) before irradiation, this may be
due to the slight quantity of lubricant on the films surface as
shown by FTIR/ATR.
From the results given in Fig. 11, it can be seen that irradiation
increased the contact angle of diiodomethane (the non-polar
solvent) with COC surface, and in the same time decreased the
contact angles for the polar one (ethylene glycol). It should be
noticed that modifications of contact angle after irradiation
were more important for the non-lubricated COC as compared
with the lubricated one especially for the high doses (75 and
150 kGy). Hence, the surface polarity of COC increased with
229
irradiation. In order to understand the above changes, these
results were correlated with those obtained with FTIR and
HPLC. Indeed, the increase of polarity after irradiation can be
correlated to the presence of surface polar groups such as
(CQO) groups evidenced by FTIR analysis for both kinds of
COC. This increase of polarity also results from the low molecular
weight polar compounds that were formed during irradiation
and that were observed by HPLC. But both analytical techniques
did not help to answer why the impact of the lubricant on surface
state of polymer was observed only after irradiation. We sug-
gested that irradiation increased the surface roughness of
polymer, and that is why these modifications were more impor-
tant for non-lubricated polymers because one of the advantages
of lubricant is to protect polymer surface from abrasion and
friction. More detailed study of surface topography by Atomic
Force Microscopy (AFM) and chemistry modification by X-ray
Photoelectron Spectroscopy (XPS) appear to be essential for
the better understanding of the effect of lubricant on surface
modification.
It should be noticed that the increase in surface polarity was in
agreement with other studies realized on COC surfaces modified
by oxygen plasma treatment (Bhattacharyya and Klapperich,
2007; Nikolova et al., 2004; Roy et al., 2010), which is known to
incorporate oxygen containing functional groups onto a polymer
surface (Hwang et al., 2008). Several examples in the literature
showed that similar oxidation mechanisms could be achieved by
electron beam irradiation (Burkert et al., 2009).
3.3. Post-irradiation ageing
Ageing of irradiated TOPASs 8007 D-61 with time was
studied. To simulate a long time ageing, an accelerated ageing
was carried out by storing the polymers at 50 1C for 1 and
6 months. After a 1 month storage, an increase in the intensity
of the CQO band at 1712 cm  1 was observed for the samples
irradiated at 75 kGy as compared with the irradiated samples
stored 4 months in fridge. For the 25 kGy irradiated samples this
increase was less clear. However no increase was observed for the
150 kGy irradiated samples. After a 6 months storage, the CQO
band intensity increased by a factor of 1.8 for the 25 kGy
irradiated polymers and by a factor of 1.2 for the 150 kGy
irradiated polymers when compared with the irradiated samples
230 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231
Fig. 12. Comparaison of the 1712 cm  1 relative absorbance for the irradiated
samples stored in the fridge and samples stored 1 and 6 months at 50 1C. Samples
were analyzed in FTIR/Transmission. Relative absorbance was defined as the ratio
at 1712 cm  1 to the CQO band absorbance for the unaged and non-irradiated
sample.
stored 4 months in fridge (Fig. 12). This process was certainly due
to the existence of trapped radicals in the polymer that reacted
with oxygen. Even if the number of trapped radicals generated by
irradiation increased with the irradiation dose, the increase of the
intensity of the CQO band after 6 months storage at 50 1C as
compared with samples stored in the fridge, was more important
for the less irradiated polymers. This phenomenon might be
explained by a favorable diffusion of oxygen after 6 months
through the polymer irradiated at 25 kGy in comparison
with higher doses due to the crosslinking occurred after irradia-
tion at 75 and 150 kGy. Our findings were partially in agreement
with the results of Saunier et al. (2008) which showed similar
increase of oxidation group in the samples stored 6 months
in the fridge when compared with freshly irradiated polymers,
but contrary to our results this increase was a function of
irradiation dose.
4. Conclusion
Electron beam radio-sterilization led to significant COC chain
modifications with predominant crosslinking, however these
modifications did not affect the thermal properties of the poly-
mer. On the contrary, the consequence of these modifications was
the generation of low molecular weight compounds such as
oligomers and degradation products of the antioxidant. Such
compounds were even found at 25 kGy, which is the maximum
dose recommended for the sterilization of medical devices and
pharmaceutical packaging. Unfortunately, low molecular weight
compounds are able to migrate from the polymer to the formula-
tions in contact with it and might induce potential toxicity.
Therefore, they must be identified and their toxicity must be
studied. Such study to identify degradation products and to
evaluate their migration into medias of different polarities under
accelerated conditions is currently in progress.
Moreover, modifications of the surface state were evidenced
after irradiation. An increase of surface polarity was observed,
more important for the non-lubricated polymers as compared
with lubricated ones. A more detailed study on the impact of
sterilization and additives on the surface state seems to be
essential because that might result in the adsorption of active
agents on the polymer surface and as a consequence it might alter
the compatibility of the polymer with the pharmaceutical
formulations destined to be stored in.
Acknowledgments
The authors would like to thank Ticona (Germany) for provid-
ing COC used in this study, as well as the Faculty of Pharmacy of
Tishreen-University (Latakia–Syria) for the research funding.
Special thanks to Vincent MAZEL for his kind help in FTIR
microscopy analysis.
References
Abraham, A.C., Czayka, M.A., Fisch, M.R., Electron beam irradiations of polypropy-
lene syringe barrels and the resulting physical and chemical property changes.
Radiat. Phys. Chem. 79, 83–92.
Allen, D.W., Clench, M.R., Crowson, A., Leathard, D.A., Saklatvala, R., 1994.
Characterisation of electron beam generated transformation products of
irganox 1010 by particle beam liquid chromatography–mass spectrometry
with on-line diode array detection. J. Chromatogr. A 679, 285–297.
Allen, D.W., Leathard, D.A., Smith, C., 1991. The effects of gamma irradiation on the
fate of hindered phenol antioxidants in food contact polymers. Analytical and
14C-labelling studies. Int. J. Radiat. Appl. Instrum. C Radiat. Phys. Chem. 38,
461–465.
Ansari, I.A., Datta, A.K., 2003. An overview of sterilization methods for packaging
materials used in aseptic packaging systems. Food Bioprod. Process. 81, 57–65.
Šećerov, B., Marinović Cincović, M.T., Popović, S., Nedić, Z., Kaćarević-popović, Z.,
2008. Characterization of gamma irradiated ethylene–norbornene copolymer
using FTIR, UV–vis and DSC Techniques. Polym. Bull. 60, 313–322.
Bhattacharyya, A., Klapperich, C.M., 2007. Mechanical and chemical analysis of
plasma and ultraviolet-ozone-surface treatments for thermal bonding of
polymeric microfluidic devices. J. R. Soc. Chem., 876–882.
Bourges, F., Bureau, G., Dumonceau, J., Pascat, B., 1992a. Effects of electron beam
irradiation on antioxidants in commercial polyolefins: determination and
quantification of products formed. Packag. Technol. Sci. 5, 205–209.
Bourges, F., Bureau, G., Pascat, B., 1992b. Effects of electron beam irradiation on
commercial polypropylene: kinetic study of antioxidant degradation. Packag.
Technol. Sci. 5, 197–204.
Buchalla, R., Begley, T.H., 2006. Characterization of gamma-irradiated polyethy-
lene terephthalate by liquid-chromatography–mass-spectrometry (LC–MS)
with atmospheric-pressure chemical ionization (APCI). Radiat. Phys. Chem.
75, 129–137.
Buchalla, R., Boess, C., Bögl, K.W., 1999. Characterization of volatile radiolysis
products in radiation-sterilized plastics by thermal desorption–gas
chromatography–mass spectrometry: screening of six medical polymers.
Radiat. Phys. Chem. 56, 353–367.
Burkert, S., Kuntzsch, M., Bellmann, C., Uhlmann, P., Stamm, M., 2009. Tuning of
surface properties of thin polymer films by electron beam treatment. Appl.
Surf. Sci. 255, 6256–6261.
Chapiro, A., 1988. Chemical modifications in irradiated polymers. Nucl. Instrum.
Meth. B 32, 111–114.
Clough, R.L., 2001. High-energy radiation and polymers: a review of commercial
processes and emerging applications. Nucl. Instrum. Methods B 185, 8–33.
Commission of the European Communities, 1990. CPMP Working Party on Quality
of Medicinal Products. Note for Guidance.
Davenas, J., Stevenson, I., Celette, N., Cambon, S., Gardette, J.L., Rivaton, A.,
Vignoud, L., 2002. Stability of polymers under ionising radiation: the many
faces of radiation interactions with polymers. Nucl. Instrum. Methods B 191,
653–661.
Gibbs, J.H., DiMarzio, E.A., 1958. Nature of the glass transition and the glassy state.
J. Chem. Phys. 28, 373.
El Mansouri, H., Yagoubi, N., Ferrier, D., 1998. Extraction of polypropylene
additives and their analysis by HPLC. Chromatographia 48, 491–496.
Fintzou, A.T., Badeka, A.V., Kontominas, M.G., Stahl, M.R., Riganakos, K.A., 2007.
Changes in physicochemical and mechanical properties of electron-beam
irradiated polypropylene syringes as a function of irradiation dose. Radiat.
Phys. Chem. 76, 841–851.
Fox, T.G., Flory, P.J., 1950. Second order transition temperatures and related proper-
ties of polystyrene. I. Influence of molecular weight. J. Appl. Phys. 21, 581.
Goldman, M., Gronsky, R., Ranganathan, R., Pruitt, L., 1996. The effects of gamma
radiation sterilization and ageing on the structure and morphology of medical
grade ultra high molecular weight polyethylene. Polymer 37, 2909–2913.
Haji-Saeid, M., Sampa, M.H.O., Chmielewski, A.G., Radiation treatment for ster-
ilization of packaging materials. Radiat. Phys. Chem. 76, 1535–1541.
Hwang, S.-J., Tseng, M.-C., Shu, J.-R., Her Yu, H., 2008. Surface modification of cyclic
olefin copolymer substrate by oxygen plasma treatment. Surf. Coat. Technol.
202, 3669–3674.
Jenke, D., 2007. Evaluation of the chemical compatibility of plastic contact
materials and pharmaceutical products; safety considerations related to
extractables and leachables. J. Pharm. Sci. 96, 2566–2581.
Kačarević-Popović Zorica, M., Š.B., Marinović-Cincović Milena, T., Nedić Zoran,
Jovanović Slobodan, M., 2006. Modification of ethylene–norbornene copoly-
mer by gamma irradiation hemijska industrija 60, 311.
Lau, O.-W., Wong, S.-K., 2000. Contamination in food from packaging material.
J. Chromatogr. A 882, 255–270.
 H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231
Majumder, P.S., Bhowmick, A.K., 1999. Surface and bulk-properties of EPDM
rubber modified by electron beam irradiation. Radiat. Phys. Chem. 53, 63–78.
Naga, N., Tsuchiya, G., Toyota, A., 2006. Synthesis and properties of polyethylene
and polypropylene containing hydroxylated cyclic units in the main chain.
Polymer 47, 520–526.
Nakade, K., Nagai, Y., Ohishi, F., 2010. Photodegradation of some ethylene–
norbornene random copolymers. Polym. Degrad. Stabil. 95, 2654–2658.
Nikolova, D., Dayss, E., Leps, G., Wutzler, A., 2004. Surface modification of cyclo
olefinic copolymers for optimization of the adhesion to metals. Surf. Interface
Anal. 36, 689–693.
Rische, T., Waddon, A.J., Dickinson, L.C., MacKnight, W.J., 1998. Microstructure and
morphology of cycloolefin copolymers. Macromolecules 31, 1871–1874.
Roy, S., Yue, C.Y., Lam, Y.C., Wang, Z.Y., Hu, H., 2010. Surface analysis, hydrophilic
enhancement, ageing behavior and flow in plasma modified cyclic olefin
copolymer (COC)-based microfluidic devices. Sensorors Actuatators B Chem.
150, 537–549.
231
Saunier, J., Aymes Chodur, C., Leclerc, B., Larbes, L., Yagoubi, N., 2008. Using COC as
pharmaceutical or cosmetic storage material. II. Effect of electron beam radio-
sterilization. J. Appl. Polym. Sci. 109, 1829–1839.
Topass, TOPAS Advanced Polymer, /www.topas.comS.
Yamazaki, M., 2004. Industrialization and application development of cyclo-olefin
polymer. J. Mol. Catal. A: Chem. 213, 81–87.
Yang, T.C.K., Lin, S.S.Y., Chuang, T.-H., 2002. Kinetic analysis of the thermal
oxidation of metallocene cyclic olefin copolymer (mCOC)/TiO2 composites by
FTIR microscopy and thermogravimetry (TG). Polym. Degrad. Stabil. 78,
525–532.
Young, M.-J., Chang, W.-S., Ma, C.-C.M., 2003. Polymerization kinetics and model-
ing of a metallocene cyclic olefin copolymer system. Eur. Polym. J. 39,
165–171.
Zhang, J., Das, C., Fan, Z., 2008. Dynamic coating for protein separation in
cyclic olefin copolymer microfluidic devices. Microfluids Nanofluids 5,
327–335.