چکیده (انگلیسی):

The purpose of this study was to
develop and evaluate a dialysis in vitro release
technique for peptide-containing poly(d, l-lactide-coglycolide)
(PLGA) microspheres (ms) that would
correlate with in vivo data. Using a luteinizing
hormone- releasing hormone analogue (LHRH),
Orntide acetate, solubility and stability were
determined in 0.1 M phosphate buffer (PB), pH 7.4,
and in 0.1 M acetate buffer (AB), pH 4.0, with highperformance
liquid chromotography (HPLC), and
peptide permeability through a dialysis membrane
(molecular weight cut-off 300,000) was determined.
Orntide ms were prepared by a dispersion/solvent
extraction/evaporation method and characterized for
drug content (HPLC), particle size distribution (laser
diffraction method), and surface morphology (scanning
electron microscopy). In vitro release was studied in
PB using a conventional extraction method and with a
new dialysis method in AB. Gravimetric analyses of
polymer mass loss and matrix hydration, and peptide
adsorption to blank PLGA ms (50:50, Mw 28 022) were
carried out in PB and AB upon incubation at 37° C.
Serum Orntide and testosterone levels in rats after
administration of Orntide ms were determined by
radioimmunoassay. Orntide acetate solubility was
influenced by pH; approximately 2.3 mg/mL dissolved
in PB and > 18 mg/mL in AB. Stability was pH- and
temperature-dependent. The peptide was very stable at
pH 4.0, 4° C, but degraded rapidly at pH 7.4, 37° C.