In the heart of Appalachia, there have long been doughty renegades who prefer not to pay taxes on their whiskey (also known as moonshine or a potential substance of abuse). These ingenious individuals have continually come up with imaginative ways to distill and distribute their products, while evading law enforcement (also known as revenuers). In fact, one of America’s favorite pastime — NASCAR — was born of the need of moonshiners to outrun the revenuers.

These days though, the game is being played the other way around. Drugmakers, with encouragement from the government, are coming up with some pretty cool ways to prevent the abuse and misuse of opioids and other prescription drugs, which have become another of American’s favorite pastimes. In 2009, 16 million Americans age 12 and older had taken a prescription pain reliever, tranquilizer, stimulant, or sedative for nonmedical purposes at least once in the year prior to being surveyed, according to the National Survey on Drug Use and Health.

Dr. Lynn Webster discussed some innovative technologies to prevent opioid misuse at the annual meeting of the American Academy of Pain Medicine. So what’s on the horizon?

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone that is indicated for once-daily administration for the management of moderate-to-severe pain in opioid-tolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period of time. The drug uses a new technology – osmotic-controlled release oral delivery system (OROS) — which uses osmosis to attract water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for the drug to release effective levels of hydromorphone and 4-5 days of use to reach a steady state of the drug in the body, said Dr. Webster.

Acurox is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox uses another new technology, this one designed to deter misuse and abuse by intentional swallowing of excess quantities of tablets, intravenous injection of dissolved tablets, and nasal snorting of crushed tablets.

Collegium Pharmaceutical is developing an extended-release opioid formulation using DETERx technology to thwart abuse. Crushing or chewing prior to ingestion is a commonly used method of abusing oxycodone. Company studies have demonstrated that the plasma profile for the new DETERx formulation pill, when chewed, was bioequivalent to the taking the pill whole and as intended. This suggests that attempting to breakdown the sustained-release microspheres by chewing would not result in a meaningful increase in plasma level.
“It’s an abuse-resistant formulation, in that [potential abusers]can’t extract more than is intended for drug delivery,” said Dr. Webster.

Perhaps the most interesting and impressive technology is being developed by PharmacoFore. According to the company, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology effectively deters prescription drug abuse at a molecular level. “This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are “activated” to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested).”

The Tennessee Valley Authority photographed this moonshine still in Knox County, Tenn. in 1936.

The system uses a mechanism “that locks in the amount of release of an opioid from a moiety, which is attached to a molecule … it can be any opioid … it’s an inert compound until it’s activated to be released,” said Dr. Webster. Essentially, the opioid molecule is attached to this delivery compound, which is ”kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will cause a process to begin … and it will allow that drug to be released.” The “clock” compound determines how much time it will take for the active compound to be released and can be attached to any opioid. “It’s very early on though,” cautioned Dr. Webster. This molecular delivery system is in phase I trials.

Still, if the drug companies are able to get these technologies approved, we could see a drop in prescription drug abuse. It remains to be seen if there will be a corresponding increase in moonshine.

— Kerri Wachter (on Twitter @knwachter)

Drug Makers Go High-Tech to Prevent Opioid Abuse