چکیده (انگلیسی):

An accelerated method to evaluate
peptide release from poly(dl-lactide-co-glycolide)
(PLGA) depot formulations in short time is
described. Peptide-loaded microspheres were made
from hydrophilic 50:50 PLGA by a dispersionsolvent
extraction technique, and peptide release
was studied at 37°C and at higher temperatures in
various media. For all accelerated conditions,
release was faster at temperatures above the glass
transition, Tg, of the host polymer. Complete
release of peptide from 8600 MW PLGA was
achieved in 35 hours at 50°C in buffered and
nonbuffered media containing 0.5% polyvinyl
alcohol (PVA). Type of release media and
concentration of PVA influenced the release
profiles. A PVA concentration of 0.1 to 0.5% was
found to prevent aggregation of microspheres at
higher temperatures, with an increase in release at
the higher PVA concentration. Peptide release was
associated with a reduction of pH of the releasing
media and increased mass loss. Complete peptide
release at pH 4 from 8.6 kd and 28 kd PLGA at 50
and 60°C occurred within 30-40 hours and
correlated well with the real-time release at 37°C
and pH 7.0. At the higher molecular weight, a
slightly longer accelerated release time and higher
temperature were required to correlate with the realtime
release. The data suggest that by optimization
of release conditions such as temperature, surfactant
concentration, buffer component, and pH, an
accelerated study could be employed to evaluate
depot formulations for a given polymer type.