A study of drug release from homogeneous PLGA microstructures

Abstract

The hydrogel template method was used to fabricate homogeneous drug–PLGA microparticles. Four drugs (felodipine, risperidone, progesterone, and paclitaxel) were loaded into the PLGA particles with the homogeneous size of 10 µm, 20 µm, and 50 µm. The drug loading into the PLGA microparticles was 50% and higher. The felodipine–PLGA microstructures of four different sizes showed that the drug release kinetics is dependent on the total surface area available for drug release. The smaller the particle size, the release rate was faster. Two types of microparticles (10 µm diameter and 10 µm height, and 50 µm diameter and 5 µm height) showed zero-order release and complete release was observed within 2 weeks. The release rate, however, was not exactly proportional to the surface area. Different drugs which were loaded into the same PLGA formulation showed different release profiles. The main difference was on the initial burst release. The overall release profile seems to be similar for different drugs, if the release profile is adjusted to eliminate the burst release. The initial burst release appears to be inversely related to the water-solubility of a drug, i.e., the lower the water-solubility of a drug, the higher the burst release. The hydrogel template method allowed preparation of homogeneous particles with predefined sizes with high drug loading. It allowed study on the effect of size and shape on the drug release kinetics. With the microparticles of homogeneous size and shape, the drug release kinetics can be projected based on the size of microparticles and water-solubility of a drug. The ability of making homogeneous particles is expected to provide better prediction and reproducibility of the drug release property of a given formulation.