AAPS PharmSciTech

, Volume 9, Issue 4, pp 1110–1118 | Cite as

γ-irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: II. Effect of Oxygen and EPR Investigation

  • R. Dorati
  • C. Colonna
  • C. Tomasi
  • I. Genta
  • T. Modena
  • A. Faucitano
  • A. Buttafava
  • B. Conti
Research Article


The purpose of this research was to evaluate how the presence of oxygen can affect irradiation-induced degradation reactions of PEGd,lPLA and PEG-PLGA multiblock copolymers submitted to gamma irradiation and to investigate the radiolytic behavior of the polymers. PEGd,lPLA, PEG-PLGA, PLA, and PLGA were irradiated by using a 60Co irradiation source in air and under vacuum at 25 kGy total dose. Mw and Mn were evaluated by gel permeation chromatography. The stability study was carried out on three samples sets: (a) polymer samples irradiated and stored in air, (b) polymer samples irradiated and stored under vacuum, and (c) polymer samples irradiated under vacuum and stored in air. The thermal and radiolytic behavior was investigated by differential scanning calorimetry and electron paramagnetic resonance (EPR), respectively. Samples irradiated in air showed remarkable Mw and Mn reduction and Tg value reduction due to radiation-induced chain scission reactions. Higher stability was observed for samples irradiated and stored under vacuum. EPR spectra showed that the presence of PEG units in multiblock copolymer chains leads to: (a) decrease of the radiolytic yield of radicals and (b) decrease of the radical trapping efficiency and faster radical decay rates. It can be concluded that the presence of oxygen during the irradiation process and the storage phase significantly increases the entity of irradiation-induced damage.

Key words

ionizing radiation multiblock copolymer polymer stability radicals radiolysis mechanism 


  1. 1.
    European Medicines Agency. The use of ionizing radiation in the manufacture of medicinal products European Guidelines 3AQ4a. (1991).Google Scholar
  2. 2.
    J. S. C. Loo, C. P. Ooi, and F. Y. C Boey. Degradation of poly(lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by electron beam radiation. Biomaterials. 26:1359–1367 (2005).PubMedCrossRefGoogle Scholar
  3. 3.
    K. J. Hemmerich. Radiation sterilization, Polymer materials selection for radiation-sterilized products. Medical Device and Diagnostic Industry MDDI Feb. 2000, p. 78.Google Scholar
  4. 4.
    J. A. Bushell, M. Claybourn, H. E. Williams, and D. M. Murphy. An EPR and ENDOR study of gamma and beta-radiation sterilization in poly(lactide-co-glycolide) polymers and microspheres. J. Control. Release. 110(1):49–57 (2005).PubMedCrossRefGoogle Scholar
  5. 5.
    R. Dorati, I. Genta, L. Montanari, A. Buttafava, A. Faucitano, and B. Conti. The effect of γ-irradiation on PLGA/PEG microspheres containing ovalbumin. J. Control. Release. 107:78–90 (2005).PubMedCrossRefGoogle Scholar
  6. 6.
    A. Faucitano, A. Buttafava, L. Montanari, F. Cilurzo, B. Conti, I. Genta, and L. Valvo. Radiation induced free radical reactions in polymer/drug systems for controlled release: an EPR investigation. Radiat. Phys. Chem. 67:61–72 (2003).CrossRefGoogle Scholar
  7. 7.
    L. Montanari, M. Costantini, E.C. Signoretti, L. Valvo, M. Santucci, M. Bortolomei, P. Fattibene, S. Onori, A. Faucitano, B. Conti, and I. Genta. Gamma-irradiations effects on poly(d,l-lactie-co-glycolide) microspheres. J. Control. Release. 56(2):219–229 (1998).PubMedCrossRefGoogle Scholar
  8. 8.
    H. J. Haugen, M. Brunner, F. Pellkofer, J. Aigner, J. Will, and E. Wintermantel. Effect of different γ-irradiation doses on cytotoxicity and material properties of porous polyether–urethane polymer. J. Biomed. Mater. Res. B. Appl. Biomate. 80B(2):415–423 (2006).CrossRefGoogle Scholar
  9. 9.
    M. Claybourn, H. Gray, D. M. Murphy, I. J. Purnell, and C. C. Rowlands. Electron magnetic resonance study of gamma-irradiated poly(lactide-co-glycolide) microspheres. J. Control. Release. 91(3):431–438 (2003).PubMedCrossRefGoogle Scholar
  10. 10.
    M. M. B. Sintzel, A. Merkli, C. Tabatabay, and R. Gurny. Influence of irradiation sterilization on polymers used as drug carriers—a review. Drug Dev. Ind. Pharm. 23(9):857–878 (1997).CrossRefGoogle Scholar
  11. 11.
    L. Martini, J. H. Collett, and D. Attwood. The influence of gamma irradiation on the physicochemical properties of a novel triblock copolymer of ε-caprolactone and ethylene oxide. J. Pharm. Pharmacol. 49(6):601–605 (1997).PubMedGoogle Scholar
  12. 12.
    R. Garcia, B. Howard, R. LaRue, G. Parton, and J. Walke. Strategies for Gamma Sterilization of Pharmaceuticals. Pharmaceutical & Medical Packaging News. PMPN May 2004.Google Scholar
  13. 13.
    M. Bernkopf. Sterilisation of Bioresorbable Polymer Implants. Medical Device Technology MDT May/June 2007.Google Scholar
  14. 14.
    M. A. Al-Ma’adeed, I. Y. Al-Qaradawi, N. Madi, and N. J. Al-Thani. The effect of gamma irradiation and shelf aging in air on the oxidation of ultra-high molecular weight polyethylene. Appl. Surf. Sci. 252(9):292 (2006).Google Scholar
  15. 15.
    R. Dorati, C. Colonna, M. Serra, I. Genta, T. Modena, F. Pavanetto, P. Perugini, and B. Conti. γ-irradiation of PEGd,lPLA and PEG-PLGA multiblock copolymers: I Effect of irradiation doses. AAPS PharmSciTech. 9(2):718–725 (2008).PubMedCrossRefGoogle Scholar
  16. 16.
    A. Gèze, M. C. Venier-Julienne, J. Cottin, N. Faisant, and J. P. Benoit. PLGA microsphere bioburden evaluation for radiosterilization dose selection. J. Microencapsul. 18(5):627–636 (2001).PubMedCrossRefGoogle Scholar
  17. 17.
    L. Woo, and C. L. Sandford. Comparison of electron beam irradiation with gamma processing for medical packaging materials. Radiat. Phys. Chem. 63:845–850 (2002).CrossRefGoogle Scholar
  18. 18.
    C. Ahlneck, and G. Zografi. The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state. Int. J. Pharm. 62(2–3):87–95 (1990).CrossRefGoogle Scholar
  19. 19.
    C. A. Oksanen, and G. Zografi. Molecular mobility in mixtures of absorbed water and solid poly(vinylpyrrolidone). Pharm. Res. 10(6):791–799 (1993).PubMedCrossRefGoogle Scholar
  20. 20.
    B. C. Hancock, and G. Zografi. The relationship between the glass transition temperature and the water content of amorphous pharmaceutical solids. Pharm. Res. 11(4):471–477 (1994).PubMedCrossRefGoogle Scholar
  21. 21.
    F. J. Buchanan, J. R. White, B. Sim, and S. Downes. The influence of gamma irradiation and aging on degradation mechanisms of ultra-high molecular weight polyethylene. J. Mater. Sci: Mater. Med. 12(1):29–37 (2001).CrossRefGoogle Scholar
  22. 22.
    M. Z. Heydari, E. Malinen, E. O. Hole, and E. Sagstuen. Alanine radicals 2. The composite polycrystalline alanine EPR spectrum studied by ENDOR, thermal annealing, and spectrum simulation. J. Phys. Chem. A. 106:8971–8977 (2002).CrossRefGoogle Scholar
  23. 23.
    D. Becker, S. Swart, and M. D. Sevilla. Electron spin resonance investigation of intramolecular hydrogen transfer and alkyl attack in ester cation radicals. J. Phys. Chem. 89(12):2638–2646 (1985).CrossRefGoogle Scholar
  24. 24.
    A. Faucitano, A. Buttafava, F. Martinotti, P. Ferloni, and A. Magistris. The mechanism of gamma-radiolysis of polymethylene, polypropylene and poly-n-butylene oxides: an ESR investigation. Radiat. Phys. Chem. 40(5):347–355 (1992).Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • R. Dorati
    • 1
  • C. Colonna
    • 1
  • C. Tomasi
    • 2
  • I. Genta
    • 1
  • T. Modena
    • 1
  • A. Faucitano
    • 3
  • A. Buttafava
    • 3
  • B. Conti
    • 1
  1. 1.Department of Pharmaceutical ChemistryUniversity of PaviaPaviaItaly
  2. 2.Department of Physical Chemistry and I.E.N.I.C.N.R.University of PaviaPaviaItaly
  3. 3.Department of Organic ChemistryUniversity of PaviaPaviaItaly

Personalised recommendations