How Do You Make A Painkiller Addiction-Proof?

In 2010, OxyContin introduced a new formula that drug abusers can't crush to a powder to snort or inject. This is how it works, chemically, and whether it actually deters abuse.

For those who have severe chronic pain, the advantage of OxyContin over other prescription painkillers is that it lasts for 12 hours. For those who like to get high on opioids, the great thing about OxyContin is that if you crush it and snort it, or mix it with water and inject it, you get 12 hours’ worth of oxycodone all at once. “So basically they get a really big high,” Bob Jamison, a professor of anesthesiology at Brigham and Women’s Hospital in Boston, tells Popular Science.

Those injectors and snorters have plenty of company. Prescription opioids—drugs that work similarly to opium, including OxyContin, Vicodin, Percocet and others—are the number-one cause of drug overdose deaths in the U.S. That includes overdoses from illegal drugs such as heroin and cocaine. In 2010, prescription opioids accounted for 44 percent of all U.S. overdose deaths. It’s a huge problem and drug companies are turning to a solution they know very well: chemistry.

Purdue Pharma first introduced OxyContin in the 1990s. The new pill combined the well-known pain reliever oxycodone with Purdue’s own long-acting formula, which slowly released oxycodone once a pill made its way into the digestive system. Because swallowed OxyContin didn’t provide a big, front-loaded hit of opioid, Purdue advertised it as nearly addiction-proof, Fortune reported. It turned out to be almost exactly the opposite.

In 2010, Purdue quietly introduced a new formula that made OxyContin pills weirdly difficult to crush or dissolve in water, hoping to undercut the ways people had discovered they could get a super-sized opioid hit from long-acting OxyContin. Three years later, studies are just beginning to show that crush-resistant chemistry does seem to reduce OxyContin abuse. Whether it reduces drug abuse overall is another question. Preliminary findings suggest those who used to abuse OxyContin are simply replacing it with other prescriptions or with heroin.

Meanwhile, researchers are working on several other ways of making painkillers physically more difficult to abuse. Nothing else is on the market yet, but the experts I talked to said to expect companies to try. “It’s a booming industry,” Jamison says.

If drug abusers respond to new formulations the way they have for OxyContin, this may mean a reduction in prescription pill abuse, although not necessarily an overall reduction in drug abuse. Instead, pharmaceutical companies will simply, finally be able to shift some blame for abuse away from their own products.

For Purdue Pharma, at least, that blame has been costly. In 2007, the company settled with U.S. federal agencies in a criminal court, paying $634 million and pleading guilty to misleading the public about OxyContin’s potential for addiction.

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The technology that goes into the new, crush-resistant, long-lasting OxyContin is called Intac, and it’s made by the German company Grünenthal. A pill made with Intac begins life a little differently than the standard tablet, says Alexander Kraus, vice president for product development at Grünenthal USA.

Most tablets start as a powder mixture that includes the active medicine and any other inactive ingredients that may, for example, help stabilize the active ingredients. Machinery presses the powder into a pill. Crushing the pill into snort-able or dissolve-able grains is just taking it back to its original form. “If you take that tablet and put it between two spoons, you typically would be able to crush it back into the powder component,” Kraus says.

OxyContin, on the other hand, starts as oxycodone, plus a plastic-like polymer material made of long-chain molecules. When heated, the polymer enters a molten phase, Kraus says. The manufacturing process forms tablets out of the hot, semi-liquid stuff and then cools them until they are solid, at which point the oxycodone is embedded in the solid polymer. The final pills have a “plasticky type of solid, monolithic form,” Kraus says.

“It’s not hard like a rock,” he says. “It has some plasticity, so if you bang on it, it will deform, but it will not shatter, and that’s the trick.”

Another cool trick? If you try to dissolve the new-formulation OxyContin in water or alcohol, it forms a thick, stringy goop that’s difficult to inject.

Other chemical blocks in different stages of research include putting little packets of opioid antagonists—think of them as opioid antidotes—into pills. If an abuser crushes the pills, he or she opens the packets, releasing the antagonists, which prevent the opioid from working. The packets are supposed to stay sealed if taken by mouth, however, so that the pills continue to work for legitimate patients.

Some companies are working on molecules that require something in the digestive system, such as an enzyme, to activate the opioid. It’s as if both the painkiller and the euphoric effect of the medicine are locked up and there’s no way to unlock them without first putting them through your entire GI tract.

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When Purdue first came out with the reformulated OxyContin, it wasn’t allowed to say the new pill was abuse-deterrent because there wasn’t yet evidence it made a difference to abusers. It sounded like it should work, but who’s to say? “Drug users can be very inventive and so your best efforts may not work very well in practice,” says Wilson Compton, director of epidemiology, services and prevention research at the U.S.’ National Institute on Drug Abuse.

Now, just enough time has passed for researchers to check the effects of having the new OxyContin on the market for a few years. This past April, the U.S. Food and Drug Administration approved an abuse deterrent claim on OxyContin’s label based on newly published scientific studies.

Nearly all of the studies were funded by Purdue. That doesn’t necessarily mean they’re biased. It’s common practice for drug companies to bankroll the surveillance of their own products, and of course Purdue would like to know if Intac actually works. It helps that there have been several studies that ask slightly different questions about Intac’s effect on abuse and together, they point toward Intac working, Compton says.

“The effect is significant and appears to be clinically meaningful,” he says.

Studies based on the industry-funded Researched Abuse, Diversion and Addiction-Related Surveillance system found that since the introduction of Intac-enabled OxyContin, the amount of the drug diverted for abuse fell by up to 60 percent. The number of poison control calls about overdosing on OxyContin fell by 42 percent. The median street value of a new OxyContin pill is 63 cents a milligram, compared to $1 a milligram for the old pill.

In one study of people treated at rehab centers, scientists from the research company Inflexxion and Purdue Pharma found that since the new OxyContin came onto the market, abuse fell by 41 percent.

One dissenting study comes from RTI International, which did not receive Purdue funding. In a nationally representative survey, the research nonprofit found OxyContin abuse rates didn’t change much after the new OxyContin appeared on pharmacy shelves. It appears un-crushable OxyContin does put off a small number of users, specifically those that seem to use crushed OxyContin and heroin interchangeably, says Scott Novak, a statistician who performed RTI International’s analysis. Take the effect to the overall population, however, and it’s not significant.

Why wouldn’t a plasticky pill put off OxyContin abusers? One possibility is that people have gotten around the Intac technology. Human ingenuity knows no bounds. Another is that not every abuser crushes his or her pills. It’s still possible to get a high, though perhaps not as big of a rush, by taking OxyContin orally. Although detailed numbers on how many people crush versus how many people swallow are difficult to come by, it’s widely acknowledged in the scientific literature that some abusers simply swallow the pills, and that they won’t be affected by the new formula.

As for those who are deterred, some preliminary numbers show that they’re replacing their pills with other drugs.

In a letter to the editor of the New England Journal of Medicine, researchers from Washington University in St. Louis and Nova Southeastern University in Florida found that in telephone interviews, the number of drug abusers who said they primarily abused OxyContin fell by 64 percent. At the same time, those same abusers reported higher rates of using other prescription opioid drugs and heroin, which is an opioid, if not a prescription one.

Richard Dart, executive director of the Researched Abuse, Diversion and Addiction-Related Surveillance program, says he also has preliminary data showing that those other abuses rise. It will be another year before he’ll have the data fully analyzed. “I think it’s clear they do go to the other drugs,” he says. “I don’t think anybody ever thought—I mean, why would they stop abusing?”

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All the researchers I talked to acknowledged abuse-deterrent OxyContin’s weaknesses in, well, actually deterring drug abuse. Yet most wanted to see chemical deterrents appear in more drugs. If it works, even a little, why not? seemed to be the attitude.

Why not indeed? Some experts have argued the new formulas may make painkillers more expensive, a cost legitimate, non-abusing patients will have to shoulder. Yet insurance companies may also find they prefer covering abuse deterrent pills because they know their money is going to legit patients, Novak argues. In reality, there’s no way to know yet how the market will react.

Researchers had hoped that when people ran into crush-resistant OxyContin, they would take the opportunity to get clean, Compton says. Instead, they sought their high in other ways, which he calls “not a particularly satisfying outcome.”

Ultimately, this is a problem that pharmaceutical chemistry can have only a small, if any, effect on. At best, drug companies working on abuse resistant formulas are covering their own liability.

“Fundamentally, I’d like to see core approaches, whether that’s treatment for the underlying addiction, or prevention to keep people from going that direction in begin with,” Compton says. “But anything that stops people from using this in a lethal way is helpful.”