Nobody likes gulping down a big pill, to the point that some people may not bother taking their medication because it's just too hard to swallow. A new system from MIT could help in that regard, by packing the same drug dose into a smaller pill.
The technology is designed specifically for use with medications that have hydrophobic (water-insoluble) molecules as their active pharmaceutical ingredient (API). According to MIT, this describes approximately 60 percent of drugs currently available, and about 90 percent of those that are in development.
Presently, those APIs are milled into nanocrystals, which are easier for human cells to absorb. Those crystals are then blended with compounds known as excipients, which help stabilize the APIs and control how they're released. A cellulose-derived polymer called methylcellulose is a popular excipient, as it dissolves quickly in water – and thus also in the body.
Unfortunately, though, the milling process is both time- and energy-intensive, plus it can negatively affect the APIs' therapeutic properties. With those limitations in mind, a team led by Prof. Patrick Doyle and graduate student Liang-Hsun Chen developed the new technique, which also results in smaller pills or tablets.
The scientists began with a hydrophobic cholesterol-lowering API by the name of fenofibrate, and dissolved it an oil called anisole. An ultrasonication process was then used to blend that API-infused oil with methylcellulose dissolved in water. The resulting mixture took the form of a nanoemulsion, meaning that it was composed of nanoscale oil droplets suspended in water, not unlike oil-and-vinegar salad dressing.
Next, tiny drops of that nanoemulsion were dripped into a hot water bath. This caused the nanoemulsion to solidify into a gel, transforming from a drop into a particle. "The particle formation is nearly instantaneous, so everything that was in your liquid drop gets converted to a solid particle without any loss," says Doyle. "After drying, we have nanocrystals of fenofibrate uniformly distributed in the methylcellulose matrix."
Those nanocrystals were subsequently crushed into a powder and compressed into tablets, utilizing standard drug-manufacturing methods. The gel can also be poured into a mold, subsequently drying into a tablet of whatever shape is desired.
When analyzed, the tablets were found to be about 60 percent fenofibrate by weight. By contrast, currently available fenofibrate tablets have a drug concentration of only around 25 percent. This means that a conventional tablet would have to be larger than one of the MIT tablets, in order to deliver the same dosage.
What's more, the fenofibrate content of the MIT tablets could reportedly be boosted even higher by increasing the nanoemulsion's oil-to-water ratio. The technology could also be adapted for use with other APIs, by using different types of oil.
"This can enable us to make more effective and smaller drugs that are easier to swallow, and that can be very beneficial for many people who have difficulty swallowing drugs," says Chen.
The research is described in a paper that was recently published in the journal Advanced Materials.
Source: MIT
