Investigation of factors influencing the hydrolytic degradation of single PLGA microparticles

Poly lactide-co-glycolide (PLGA) is an important polymer matrix used to provide sustained release across a range of active pharmaceutical ingredients (APIs) and works by hydrolytic degradation within the body, thereby releasing entrapped drug. Processing and sterilisation can impact on the morphology and chemistry of PLGA therefore influencing the hydrolysis rate and in turn the release rate of any entrapped API. This paper has looked at the effect of supercritical carbon dioxide (scCO2) processing, gamma irradiation, comonomer ratio and temperature on the hydrolysis of individual PLGA microparticles, using a combination of Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) imaging, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetery (DSC) and Gel Permeation chromatography (GPC) to facilitate a better understanding of the physiochemical factors affecting the hydrolysis rate. This work has shown that scCO2 processing influences hydrolysis rates by increasing the porosity of the PLGA microparticles, increasing the lactide comonomer ratio decreases hydrolysis rates by reducing the hydrophilicity of the PLGA microparticles and increasing the gamma irradiation dose systematically increases the rate of hydrolysis due to reducing the overall molecular weight of the polymer matrix via a chain scission mechanism. Moreover this work shows that ATR-FTIR imaging facilitates the determination of a range of physicochemical parameters during the hydrolysis of a single PLGA microparticle including water ingress, water/polymer interface dimensions, degradation product distribution and hydrolysis rates for both lactide and glycolide copolymer units from the same experiment.