Release mechanisms of PLGA microparticles prepared using a microfluidics device or a beaker

The aim of this study was to better understand the release mechanisms of poly(lactic-co-glycolic acid) (PLGA) microparticles prepared via emulsification - solvent extraction/evaporation using a “classical beaker” vs. a “microfluidics device”. Ibuprofen-loaded microparticles were studied by optical microscopy, SEM, X-ray powder diffraction, X-ray μCT and drug release measurements from single microparticles in well agitated phosphate buffer pH 7.4 or agarose gel (mimicking living tissue). The use of a microfluidics device facilitated the preparation of microparticles with a less broad size distribution. However, in addition to the microparticle size, the inner system structure was found to be also of utmost importance for the resulting drug release kinetics in this case. Interestingly, even microparticles with similar size, composition and inner & outer structure exhibited a broad spectrum of individual drug release patterns. This was true, irrespective of the type of preparation method and experimental release set-up, and could be explained as follows: The investigated microparticles were characterized by a continuous inner pore network and an initially smooth & non-porous surface. Drug release set on as soon as: (i) the pore network got direct access to the release medium (e.g., due to a “weak point” in the PLGA surface layer), or (ii) substantial system swelling started (after a lag-time of several days). Importantly, each microparticle had its own, specific structure, which determined “its way” to release the drug. Furthermore, the experimental conditions were found to be of key importance: The presence of a surrounding agarose gel protected the microparticles from damage caused by convective fluid flow, and hindered microparticle swelling, thus, slowing down drug release.