(679e) Microfluidic Platform to Study the Effect of Mass Transfer Dynamics on the Morphology of Drug-Loaded Polymer Microparticles.

Polymer microparticles are typically used as carriers of active pharmaceutical ingredients (drugs) in many sustained-release drug delivery treatments. Solvent extraction is a well-known industrial process for preparing such drug-loaded polymer microparticles. In this process, polymer solution drops are emulsified in a bulk aqueous medium and the solvent is extracted from the polymer solution drops, thus creating polymer microparticles loaded with the drugs of choice. The extraction rate of the solvent is a crucial parameter that impacts the morphology and the porosity of the microparticle, and these properties, in turn, affect the drug release kinetics. Hence, it is crucial to understand the effect of shear on the extraction rate and the morphology of the microparticle.

The primary goal of our work is to develop a systematic framework to study the dynamic change in the morphology of a polymer solution drop under continuous flow. We have used a microfluidic extensional flow device (MEFD) to hydrodynamically trap one drop at a time and observe the dissolution process under a constant strain rate. For our experiments, we used polymer solution droplets of a biocompatible polymer, poly-lactic-co-glycolic acid (PLGA) with ethyl acetate (EtOAc) as the solvent, and solutions of polyvinyl alcohol (PVA) in water as the suspending aqueous medium. Piroxicam and rhodamine-B chloride were chosen as the model drugs to study the effect of their differences in solubility in the solvent and aqueous phase on the final drug distribution in the microparticle. We used brightfield and confocal fluorescence microscopy to observe the dynamic phase separation and microparticle formation process.

Using a mass transfer model, we theoretically describe the dissolution process for our systems. We found a close agreement between our experimental results and our theoretical predictions of dissolution rates and inferred that the extraction dynamics is primarily limited by the mass transport in the suspending aqueous phase. We also observed two distinct types of microparticle morphology for the same type and concentration of drug in the polymer solution drops. Based on the rate of solvent extraction and the rate of phase separation within the drop, we observed two types of morphologies – one in the form of a ‘core-shell’ configuration of the drug and the polymer, and the second in the form of a ‘Janus’ type of microparticle, and both these configurations are physically explained. The fluorescence microscopy images confirm the composition of the microparticle in both configurations. The results obtained from these experiments will be instrumental in developing a comprehensive model capable of predicting extraction rates and polymer microparticle morphology, which can be applied across various drug manufacturing processes in the pharmaceutical industry.