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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 steam autoclaving or dry heat that can damage materials, induce
degradation and lead to losses of both shape and mechanical
Cyclic olefin copolymers (COC) belong to a new class of properties.
amorphous polymers having remarkable combination of proper- However, the high-energy electrons released from the inter-
ties such as high transparency, low moisture uptake, glass-like action of electron beam particles with materials are known to
texture, very high heat resistance and good chemical resistance create reactive intermediates and free radicals which follow
(Naga et al., 2006; Rische et al., 1998; Yang et al., 2002; Young several reaction paths and results in crosslinking and/or scission
et al., 2003). These unique properties make COC interesting for of the polymer chains (Chapiro, 1988; Clough, 2001; Davenas
numerous industrial applications and notably in medical and et al., 2002). This can modify the mechanical properties as well as
pharmaceutical fields (Yamazaki, 2004; Zhang et al., 2008). the surface properties of the polymer (Majumder and Bhowmick,
Indeed, COC are more and more used as medical devices and 1999). In addition to that, chain scissions cause the production of
pharmaceutical packaging especially for injectables formulations low molecular weight compounds (LMWC) (Buchalla and Begley,
(Topass) which require a suitable and reliable sterilization 2006; Buchalla et al., 1999; El Mansouri et al., 1998), which are
process. susceptible to migrate from the bulk of polymer onto its surface
Electron beam irradiation has been used to sterilize medical and then to the surrounding medium (Bourges et al., 1992a; Lau
goods for well over 50 years (Abraham et al.; Ansari and Datta, and Wong, 2000). Such kind of surface modification and/or
2003; Fintzou et al., 2007; Haji-Saeid et al.). Because of its migration of leachables may affect the compatibility of the
convenience and lower cost, it provides an interesting and prefer- couple: content/container, which is an important safety require-
able alternative sterilization method towards high temperature ment in the field of pharmaceutical packaging (Jenke, 2007).
Furthermore degradation process may continue during post-
n
irradiation shelf-life storage due to the trapped free radicals that
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
are able to react even when the irradiation has been performed
Châtenay-Malabry, France. Tel.: þ 33 1 46 83 57 74; Fax: þ33 1 46 83 59 63. since a long time (Goldman et al., 1996). It should be noticed that
E-mail address: hala.barakat@u-psud.fr (H. Barakat). 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 granules. In the case of contact angle measurements and post-
treatment before, during and after irradiation (irradiation dose, sterilization ageing studies, films were used. FTIR Microscopy
irradiation atmosphere and the amount of antioxidants added to analyses were performed on granules and plates.
the polymer).
The aim of this work was firstly to study the effect of electro- 2.2. Sample irradiation
beam radio-sterilization on cyclic olefin copolymers both in the
bulk and on the surface of the material, then to investigate the Samples were irradiated by an electron beam produced by a
impact of the presence of a lubricant on surface modifications high power generator (10 MeV) from a 10 kW power accelerator
induced by irradiation, and finally to evaluate post-irradiation (Ionisos, Fr.). Samples were exposed to three different irradiation
ageing behavior. We focused on the following: doses: 25, 75, and 150 kGy. They were packed under ambient
condition in plastic (small bags) sachets.
Modification of polymer chains (oxidation, scission and cross-
linking) that might change the mechanical properties of COC
2.3. Sample storage
and generate potential leachables like oligomers.
Degradation of the antioxidant that could create compounds of
Irradiated samples were stored in the fridge (5 1C) to reduce
potential toxicity.
the post-sterilization ageing effects. Post-sterilization ageing was
A preliminary study of surface modifications after irradiation
studied by storing some of the samples at 50 1C during several
by contact angle measurements, comparison of lubricated and
weeks.
non-lubricated polymer.
Effect of accelerated post-irradiation ageing on polymer
2.4. Size Exclusion Chromatography
oxidation.
2.6. FTIR
2.10. HPLC
volume of about 9.8 mL, which was characteristic of a new transition temperature was observed with the irradiation dose
distribution of higher molecular weight. (Fig. 5). This weak decrease (1 1C for 150 kGy sample) could be
These findings were similar to the results obtained by explained in part by the increase in chain ends because of
J. Saunier (Saunier et al., 2008) who showed a predominance of branching (Gibbs and DiMarzio, 1958; Fox and Flory, 1950).
crosslinking of non-lubricated TOPASs 8007 after electron beam
irradiation.
Fig. 3. SEC chromatogram of TOPASs 8007 D-61 solution for the different Fig. 5. Evolution of the glass transition temperature with irradiation dose for
irradiated doses. TOPASs 8007 D-61 (n¼3).
Fig. 4. Evolution of polydisperty Index Ip (a) and molecular weight Mn (b) Mz (c) and Mw (d) (n¼ 3).
H. Barakat et al. / Radiation Physics and Chemistry 84 (2013) 223–231 227
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.
3.2.1. 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) 223–231 229
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.
Acknowledgments
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