Early development drug formulation on a chip: Fabrication of nanoparticles using a microfluidic spray dryer

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Keywords

microfluidics, drug delivery, spray drying

Summary

The authors have created a microfluidic device for the efficient formulation of drug substances. The device combines one or two different solvents to create a nanosuspension of a drug and sprays small droplets of this suspension onto a substrate, where the droplets dry and the drug assembles in amorphous aggregates.


Device.png

Microfluidic device made on a poly(dimethylsiloxane) (PDMS) chip. Solvent 1, containing the drug, is contained in the lower compartment. The middle compartment can be filled with a second solvent to be added to the drug mixture. The top compartment contains air, so that the final mixture can be sprayed out of the nozzle of the device (bottom).


This device has several remarkable features. First of all, it is very efficient; almost all of the volume of the solvents is contained in the final product. The final product itself is produced in a form with a very high surface-to-volume ratio, which enhances bioavailability since it means that more drug molecules can be in contact with the environment they are supposed to interact with. This is achieved by the use of very small droplets (~4μm) in the drug spray and by the insertion of a crystallization inhibitor (PVP - poly(vinyl-pyrrolidone)) in the second solvent compartment, which prevents the sprayed droplets from drying in a crystalline arrangement when they reach the substrate. Finally, the production method of this apparatus, which is based on lithography, is scalable and cheap.


Drug aggregate.png

Image of the final drug product. The substance is amorphous; this was achieved by the addition of PVP in the drug nanosuspension, which prevents crystallization.