Analysis of residual solvents in poly(lactide- co -glycolide) nanoparticles

Biodegradable nanoparticles formulated from poly(lactide- co -glycolide) (PLGA) have been extensively investigated for drug delivery. The emulsification-solvent evaporation method for manufacturing PLGA nanoparticles is simple and reproducible, but the organic solvent, dichloromethane, has undesirable environmental and safety risks. Dichloromethane is also a suspected carcinogen and mutagen, so has to be completely removed from the nanoparticles. The International Committee for Harmonization suggests a limit of residual dichloromethane of no more than 600 ppm. Here, we evaluate the residual quantity of volatile dichloromethane after the manufacturing process of nanoparticles. We developed a simple, fast, and reliable method by gas chromatography with a flame ionization detector to determine dichloromethane levels. This method was validated according to regulatory requirements and produced acceptable results with respect to specificity, linearity, sensitivity, precision, and accuracy. We also tested the effects of various parameters in the preparation of the nanoparticles such as surfactant concentration, organic phase volume, and washing frequency. This study provides a useful method for manufacturing PLGA nanoparticles with minimal residual solvent by decreasing surfactant concentration or increasing washing frequency.