Pharmaceutical Research

, Volume 12, Issue 6, pp 851–856

Gamma Irradiation Effects on Molecular Weight and in Vitro Degradation of Poly(D,L-Lactide-CO-Glycolide) Microparticles

  • Angela G. Hausberger
  • Richard A. Kenley
  • Patrick P. DeLuca
Article

DOI: 10.1023/A:1016256903322

Cite this article as:
Hausberger, A.G., Kenley, R.A. & DeLuca, P.P. Pharm Res (1995) 12: 851. doi:10.1023/A:1016256903322

Abstract

Purpose. The objective of the reported work was to quantitatively establish γ-irradiation dose effects on initial molecular weight distributions and in vitro degradation rates of a candidate credible biopolymeric delivery system.

Methods. Poly(D,L-lactide-co-glycolide) (PLGA) porous microparticles were prepared by a phase-separation technique using a 50:50 copolymer with 30,000 nominal molecular weight. The microparticles were subjected to 0, 1.5, 2.5, 3.5, 4.5, and 5.5 Mrad doses of γ-irradiation and examined by size exclusion chromatography (SEC) to determine molecular weight distributions. The samples were subsequently incubated in vitro at 37°C in pH 7.4 PBS and removed at timed intervals for gravimetric determinations of mass loss and SEC determinations of molecular weight reduction.

Results. Irradiation reduced initial molecular weight distributions as follows (Mn values shown parenthetically for irradiation doses): 0 Mrad (Mn = 25200 Da), 1.5 Mrad (18700 Da), 2.5 Mrad (17800 Da), 3.5 Mrad (13800 Da), 4.5 Mrad (12900 Da), 5.5 Mrad (11300 Da). In vitro degradation showed a lag period prior to zero-order loss of polymer mass. Onset times for mass loss decreased with increasing irradiation dose: 0 Mrad (onset = 3.4 weeks), 1.5 Mrad (2.0 w), 2.5 Mrad (1.5 w), 3.5 Mrad (1.3 w), 4.5 Mrad (1.0 w), 5.5 Mrad (0.8 w). The zero-order mass loss rate was 12%/week, independent of irradiation dose. Onset of erosion corresponded to Mn = 5200 Da, the point where the copolymer becomes appreciably soluble.

Conclusions. The data demonstrated a substantial effect of γ-irradiation on initial molecular weight distribution and onset of mass loss for PLGA, but no effect on rate of mass loss.

poly(D,L-lactide-co-glycolide) polyester degradation gamma irradiation polymer mass loss 

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Angela G. Hausberger
    • 1
  • Richard A. Kenley
    • 2
  • Patrick P. DeLuca
    • 3
  1. 1.Pfizer, Inc.Groton
  2. 2.Amylin Pharmaceuticals, Inc.San Diego
  3. 3.College of PharmacyUniversity of KentuckyLexington
  4. 4.College of PharmacyUniversity of KentuckyLexington

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