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Polymer Bulletin

, Volume 66, Issue 8, pp 1063–1073 | Cite as

The effect of aliphatic esters on the formation and degradation behavior of PLGA-based in situ forming system

  • A. MashakEmail author
  • H. Mobedi
  • F. Ziaee
  • M. Nekoomanesh
Original Paper

Abstract

The purpose of this study was to investigate the effect of three aliphatic esters, ethyl heptanoate, methyl heptanoate, and ethyl nonanoate on the in vitro degradation behavior of in situ forming systems. In situ forming implants based on 33% (w/w) poly (lactide-co-glycolide) (PLGA)/57% (w/w) N-methyl-2-pyrrolidone (NMP)/10% (w/w) esters were prepared after injection of the final formulation in phosphate buffer solution (pH 7.4, 0.2 M) at 37 °C. The influence of additives on the implants formation, morphology, and also on their in vitro degradation behaviors over a period of 45 days was investigated. The degraded matrices were evaluated to determine morphological analysis by SEM and 1H-NMR study. The solution of degradation medium was studied to indicate NMP removal and altering acidity. The results showed that the additives generated a high porous structure and caused the fast phase inversion. However, the 1H-NMR spectra indicated that ester additives remained in the matrices during degradation periods. The results of the acidity study showed that the degradation rates in the matrices containing esters were higher than the control matrix. In addition, it is shown that esters with lower molecular weight have affected the polymer degradation more efficiently than higher molecular weight esters.

Keywords

In situ forming systems Biodegradation Solvent removal Morphology Poly (lactide-co-glcolide) Aliphatic esters 

References

  1. 1.
    Ruel-Gariepy E, Leroux JC (2004) In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm 58:409–426CrossRefGoogle Scholar
  2. 2.
    Bakhshi R, Vasheghani-Farahani E, Mobedi H, Jamshidi A, Khakpour M (2006) The effect of additives on naltrexone hydrochloride release and solvent removal rate from an injectable in situ forming PLGA implant. Polym Adv Technol 17:354–359CrossRefGoogle Scholar
  3. 3.
    Astaneh R, Erfan M, Barzin J, Mobedi H, Moghimi HR (2008) Effects of ethyl benzoate on performance, morphology, and erosion of PLGA implants formed in situ. Adv Polym Technol 27:17–26CrossRefGoogle Scholar
  4. 4.
    Hatefi A, Amsden B (2002) Biodegradable injectable in situ forming drug delivery systems. J Control Release 80:9–28CrossRefGoogle Scholar
  5. 5.
    Kranz H, Bodmeier R (2007) A novel in situ forming drug delivery system for controlled parenteral drug delivery. Int J Pharm 332:107–114CrossRefGoogle Scholar
  6. 6.
    Korber M, Bodmeier R (2008) Development of an in situ forming PLGA drug delivery system: I. Characterization of a non-aqueous protein precipitation. Eur J Pharm Sci 35:283–292CrossRefGoogle Scholar
  7. 7.
    Dunn RL, English JP, Cowsar DR, Vanderbelt DP (1990) Biodegradable in situ forming implants and methods of producing the same. US Patent 4,938,763Google Scholar
  8. 8.
    Siepmann J, Gopferich A (2001) Mathematical modeling of bioerodible, polymeric drug delivery systems. Adv Drug Deliv Rev 48:229–247CrossRefGoogle Scholar
  9. 9.
    Houchin ML, Topp EM (2008) Chemical degradation of peptides and proteins in PLGA: a review of reactions and mechanisms. J Pharm Sci 97:2395–2404CrossRefGoogle Scholar
  10. 10.
    Chandrashekar BL, Zhou M, Jarr EM, Dunn RL (2000) Controlled release liquid delivery compositions with low initial drug burst. US Patent 6,143,314Google Scholar
  11. 11.
    Jain RA, Rhodes CT, Railkar AM, Malick AW, Shah NA (2000) Controlled release of drugs from injectable in situ formed biodegradable PLGA microspheres: effect of various formulation variables. Eur J Pharm Biopharm 50:257–262CrossRefGoogle Scholar
  12. 12.
    Mobedi H, Nekoomanesh M, Orafaei H, Mivehchi H (2006) Studying the degradation of poly(l-lactide) in presence of magnesium hydroxide. Iran Polym J 15:31–39Google Scholar
  13. 13.
    Houchin ML, Neuenswander SA, Topp EM (2006) Effect of excipients on PLGA film degradation and on the stability of an incorporated peptide. J Control Release 117:413–420CrossRefGoogle Scholar
  14. 14.
    Ara M, Watanabe M, Imai Y (2002) Effect of blending calcium compounds on hydrolytic degradation of poly (dl-lactic acid-co-glycolic acid). Biomaterials 23:2479–2483CrossRefGoogle Scholar
  15. 15.
    Siegel SJ, Kahn JB et al (2006) Effect of drug type on the degradation rate of PLGA matrices. Eur J Pharm Biopharm 64:287–293CrossRefGoogle Scholar
  16. 16.
    Takenaga M, Yamaguchi Y et al (2002) A novel sustained-release formulation of insulin with dramatic reduction in initial rapid release. J Control Release 79:81–91CrossRefGoogle Scholar
  17. 17.
    Dunn RL, Tipton AJ (1997) Polymeric compositions useful as controlled release implants. US Patent 5,702,716Google Scholar
  18. 18.
    Zare M, Mobedi H et al (2008) Effect of additives on release profile of leuprolide acetate in an in situ forming controlled release system: in vitro study. J Appl Polym Sci 107:3781–3787CrossRefGoogle Scholar
  19. 19.
    McHugh AJ (2005) The role of polymer membrane formation in sustained release drug delivery systems. J Control Release 109:211–221CrossRefGoogle Scholar
  20. 20.
    Brodbeck KJ, Pushpala S, McHugh AJ (1999) Sustained release of human growth hormone from PLGA solution depots. Pharm Res 16:1825–1829CrossRefGoogle Scholar
  21. 21.
    Graham PD, Brodbeck KJ, McHugh AJ (1999) Phase inversion dynamics of PLGA solutions related to drug delivery. J Control Release 58:233–245CrossRefGoogle Scholar
  22. 22.
    Hawley’s Condensed Chemical Dictionary (11th edn). Van Nostrand Reinhold Co., NY, NY, pp 224, 555, 567Google Scholar
  23. 23.
    Schwach G, Oudry N, Delhomme S, Luck M, Lindner H, Gurny R (2003) Biodegradable microparticles for sustained release of a new GnRH antagonist. Part I: screening commercial PLGA and formulation technologies. Eur J Pharm Biopharm 56:327–336CrossRefGoogle Scholar
  24. 24.
    http://www.boehringer.com/. www.resomer.com. Boehringer Ingelheim Pharma GmbH & Co. KG. Accessed 20 Oct 2009
  25. 25.
    Zhang X, Wyss UP, Pichora D, Goosen MFA (1994) Investigation of poly(lactic acid) degradation. J Bioact Compat Polym 9:80–100CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • A. Mashak
    • 1
    Email author
  • H. Mobedi
    • 1
  • F. Ziaee
    • 2
  • M. Nekoomanesh
    • 3
  1. 1.Department of Novel Drug Delivery SystemsIran Polymer and Petrochemical InstituteTehranIran
  2. 2.Department of Polymer Science and SynthesisIran Polymer and Petrochemical InstituteTehranIran
  3. 3.Department of EngineeringIran Polymer and Petrochemical InstituteTehranIran

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