Industrial-strength Pharmaceutical Assembly LineTony Pallone | May 11, 2018
The chemical composition of pharmaceuticals isn’t their only important aspect; also crucial is packaging into specific physical formulations. Many drugs, for instance, depend on encapsulation in solid microparticles of exact sizes and shapes that determine the timing and delivery of drug release.
Not surprisingly, consistency is key. But common drug manufacturing techniques, such as spray drying and ball milling, produce uneven results. The ideal method involves microfluidics — a kind of “liquid assembly line” that individually drips out microparticles of the perfect size. The microfluidic network of microscopic channels and chambers allows fine-tuning of surface tension and drag forces.
Scaling up microfluidic systems, however, has proved challenging because of the dependence on tightly controlled flow rates; typical rates are one milliliter per hour, far too slow for industrial use.
"The bottleneck for increasing the throughput of microfluidics is a fundamental physics problem," said David Issadore, an assistant professor of bioengineering at the University of Pennsylvania. "We cannot run the individual microfluidic devices faster than any other lab, because the microfluidic phenomenon that enables the drug microparticles to be precisely fabricated stops working above a critical flow rate — they go from making bubbles to making unstable jets."
But a team led by Issadore and postdoctoral researcher Sagar Yadavali has looked to another way to scale up production — increasing not the flow rate, but the number of microfluidic devices used. Their innovative fluidic architecture is similar to the technology used to manufacture computer chips, and can run more than 10,000 of these assembly lines in parallel — all on a single silicon-and-glass chip that can fit into a shirt pocket.
The team used lithography to simultaneously etch 10,260 devices into a four-inch silicon wafer, sandwiching it between two glass plates to make hollow channels, and hooking up its single sets of inlets and outlets. The result is an effective flow rate more than ten thousand times faster than what can be typically achieved in a microfluidic device.
Currently, the Penn team is testing their system with David Lai, a research investigator at pharmaceutical company GlaxoSmithKline. Issadore said the team is also working to implement additional microfluidic operations onto their chip — including miniaturized versions of solvent extraction, crystallization and other traditional chemical engineering processes. "By bringing more of the operations necessary to formulate the drug onto our chip, precise 'designer' microparticle drug formulations can be produced at an industrial scale," he said.