Use of DSC to Study the Degradation Behavior of PLA and PLGA Microparticles

Poly (D, L-lactide) (PLA) and poly (D, L-lactide-co-glycolide) (PLGA) microparticles were evaluated for their in vitro degradation behavior in 0.1 M phosphate buffer pH 7.4 at 37°C. The influence of polymer characteristics, particle size, and preparation technique was investigated. Differential scanning calorimetry (DSC) was used to follow the time-dependent physical and morphological changes within the hydrated and dried microparticles, to determine the physical state of the absorbed water, and to detect penetration of buffer ions into the particle bulk. Results were compared with degradation kinetics obtained by gel permeation chromatography (GPC) and gravimetry. The latter revealed triphasic degradation profiles for R 202 and RG 755 microparticles with a mean particle size of 55 μm and 60 μm, respectively. An induction period was followed by a period of accelerated ester cleavage pre-onset of erosion and a final period of slow ester cleavage post-onset of erosion. According to DSC data the induction period is characterized by a glassy hydrated polymer matrix with a TgH > 37°C. The induction period (ti) correlated well with the lag-time of TgH to reach 37°C (tlag 37°C), thus confirming the importance of chain mobility for the degradation kinetic. The final decrease in the rate of ester chain cleavage post-onset of erosion turned out to be the result of an increase in matrix permeability for buffer ions inducing sodium salt formation and phase separation of the water-soluble degradation products within the particle bulk. Particle size effects depended on the preparation technique. A decrease in the degradation rate with a decrease in mean particle size was only observed when the molecular weight distribution of the polymer was not affected by the prepa ration procedure used to reduce the particle size. According to DSC data, the effect is due to a faster and more continuous release of the water-soluble degradation products from the smaller particles, thus reducing their plasticizing and autocata-lytic effects within the particle bulk.