Hk. Sah et Yw. Chien, EFFECTS OF H+ LIBERATED FROM HYDROLYTIC CLEAVAGE OF POLYESTER MICROCAPSULES ON THEIR PERMEABILITY AND DEGRADABILITY, Journal of pharmaceutical sciences, 84(11), 1995, pp. 1353-1359
Microcapsules prepared from blends of poly(d,l-lactide-co-glycolide) w
ith a lactide:glycolide ratio of 75:25 (PLGA75:25) and poly(d,l-lactid
e) (PLA5000) or poly(d,l-lactic acid-co-glycolic acid) (PLGA5000) were
dispersed in phosphate-buffered saline, and their hydrolytic rates we
re investigated. Using the Henderson-Hasselbalch equation and an L-lac
tic acid experiment, the concentration of hydrogen ions released into
the bulk medium was calculated from the change in buffer pH. The rate
of H+ formation was found to be dependent upon the polymer composition
of the microcapsules. The incorporation of PLGA5000 or PLA5000 into P
LGA75:25 microcapsules drastically enhanced hydrolytic rates of microc
apsules and resulted in controlled release of hydrogen ions generated
from carboxyl end groups of both intact and degrading polymers. In con
trast to microcapsules prepared with PLGA75:25 only, which liberated a
negligible amount of H+ ions after a 21-day incubation, the microcaps
ules prepared from polymer blends released approximately (19.2-42.0) (
x10(-3)) mmol of H+ ions. It has been found that the amount of hydroge
n ions liberated into the bulk can be used as a qualitative indicator
to monitor the change in microcapsule permeability to protein as well
as polymer degradation.