Effect of gamma-irradiation on peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) microspheres.
The effect of gamma-irradiation on the physicochemical properties of peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) (PLGA) microspheres was evaluated. PLGA (50/50, Mw: 8,600) with free carboxylic end groups was used to make drug-loaded and placebo microspheres by a solvent extraction evaporation method. Both formulated and non-formulated microspheres were gamma-irradiated at 0, 1, 1.5, and 2.5 Mrad doses. HPLC analysis based on extraction of peptide from the microspheres showed that peptide content of the microspheres was lowered upon irradiation and the reduction was more pronounced in formulated microspheres. The in-vitro release in 0.033M phosphate buffer, pH 7.0 at 37 degrees C (based on extraction of residual peptide) showed that the initial and subsequent release of peptide was higher in gamma-irradiated microspheres during the first 20 days. The difference became insignificant during the erosional controlled release of the peptide. There was no difference in release between the formulated and non-formulated microspheres of the nonirradiated or irradiated forms. Molecular weights (Mw and Mn), determined by size exclusion chromatography, were reduced by gamma-irradiation for both formulated and non-formulated placebo microspheres. Differential scanning calorimetry showed a gradual reduction in Tg of placebo microspheres but no reduction in peptide-loaded microspheres. In-vivo evaluation of the nonirradiated and the 1.5 Mrad irradiated microspheres showed no marked differences through 28 days. Since irradiation caused a lowering of Mw and Mn with the appearance of a low amount of unidentified substances, seemingly catalyzed by the polymer and the formulation excipients, gamma-irradiation sterilization of these parenteral delivery systems requires careful investigation on an individual product basis.
Shameem
M
M
College of Pharmacy, University of Kentucky, Lexington 40536, USA.
Lee
H
H
Burton
K
K
Thanoo
B C
BC
Deluca
P P
PP
D005720:Gamma Rays; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid