The Triple Helix @ UChicago

Fall 2016

"Opioid Abuse Deterrence: Where Does Big Pharma Draw the Line?" by Alborz Omidian

 

One of the biggest challenges facing pharmaceutical companies that specialize in opioids, or pain medications, is the dilemma of manufacturing effective, sustainable drug formulations for patients while simultaneously making their medications resistant to tamper and abuse. Modern pain medications largely operate via an extended release mechanism, meaning that their active ingredient is designed to be released into the bloodstream at a controlled concentration over a long period of time, providing extended pain relief. 

Naturally, this creates an opportunity for individuals to tamper with medications to ingest larger doses. Pharmaceutical companies have a vested interest in minimizing the potential risks associated with their products and take steps to formulate medications that are both effective as a drug and resistant to abuse. In other words, the ideal pain medication from the perspective of a pharmaceutical company would provide immediate and prolonged relief to a patient who has undergone a painful surgical operation for example, but is also resistant to tampering via crushing, breaking apart, or other attempts to extract its active ingredient for the sake of abuse. 

How is this delicate balance achieved? The production of modern pain medications includes a wide range of abuse deterrent technologies. For example, a common method of abusing opioids is to either snort (insufflate) the product or to administer it via direct injection.[1] Both of these methods first require the crushing of the medication into a fine powder, because it is usually obtained in tablet form. As such, syntheses of many currently available drugs incorporate some type of crush resistance or crush deterrence into their design by enhancing the mechanical strength of the pill to resist physical transformations such as chewing, cutting, and grinding.[2] 

Other technologies are more creative and less obvious. For example, one of the most common methods for abusing a previous formulation of OxyContin was to prepare it for injection by crushing and then dissolving in an aqueous solution.[3] As such, reformulated OxyContin, which is currently on the market, is produced as a solid tablet matrix (matrix referring to the part of the tablet that encapsulates the active ingredient) with chemical properties that both resist mechanical stress and deter injection by turning the active ingredient into a highly viscous gel upon contact with water.[4] Other abuse deterrent technologies work by incorporating an opioid antagonist as part of the tablet matrix itself.[5] If a patient takes the medication as intended by ingesting the tablet whole, then the opioid antagonist is never released into the bloodstream, and the patient receives pain relief as intended. However, any attempt to tamper with the tablet itself releases the antagonist from the tablet matrix, mixes it with the active ingredient, and deactivates the opioid, preventing abuse. 

However, attempts to circumvent abuse deterrent technologies are often as ingenious as the technologies themselves. Some include using solutions of acetone and other common household products to chemically extract active ingredients from tablets without actually tampering with them[6], such as suspending opioid formulations in solutions of Coca-Cola or precisely cracking the outer layer of tablet to increase how much of the active ingredient can be absorbed into the bloodstream at once without activating the release of opioid antagonists.[7] Though the sources for these tampering methods are usually from online forums discussing abuse methods and are highly questionable, they do signify that pharmaceutical companies must constantly develop new, innovative technologies to prevent the abuse of their products. Unfortunately, there are drawbacks to this focus. In an attempt to lower the potency of their drugs to discourage abuse, pharmaceutical companies sometimes make their medications too weak for individuals who suffer from intense, chronic pain and require a higher dose of pain relief than the average user. These individuals often resort to self-medication and are often the same people who communicate online about attempts to bypass abuse deterrent technologies. 

Where do pharmaceutical companies draw the line? How does an organization decide on prioritizing abuse deterrence for certain individuals versus the actual efficacy of their medications for the common patient? Is there a win-win solution for both of these issues, or must they constantly be weighted against one another in never-ending competition? Furthermore, what justifications do private corporations have to control individuals and their choices to put certain substances into their bodies? As the influence of commercial medication becomes more prominent and pervasive in the coming years, it may be pertinent for future researchers and healthcare professionals to tackle these dilemmas directly. 

References

[1] Surratt H, Kurtz SP, Cicero TJ. 2011. “Alternate routes of administration and risk for HIV among prescription opioid abusers.” J Addict Dis 30: 334-341. 
[2] Mastropietro, DJ. Omidian H. 2013. “Current approaches in tamper-resistant and abuse-deterrent formulations.” Drug Dev Ind Pharm 39: 611-624. 
[3] Schneider, JP. Matthews, M. Jamison, RN .2010. “Abuse-deterrent and tamper-resistant opioid formulations: what is their role in addressing prescription opioid abuse?” CNS Drugs 24: 805-810. 
[4] Pappagallo, M. Sokolowska, M. 2012. “The implications of tamper-resistant formulations for opioid rotation.” Postgrad Med 124: 101-109. 
[5] Colucci, SV. Perrino, PJ. Shram, M. Bartlett, C. Wang, Y. et al. 2014. “Abuse potential of intravenous oxycodone/naloxone solution in nondependent recreational drug users.” Clin Drug Investig 34: 421-429. 
[6] bluelight.org. 2010. “Experiment Thread New Formulation Oxycodone Extraction” Last modified may 2011. http://www.bluelight.org/vb/threads/523580-Experiment-Thead-New-Formulation-Oxycodone-Extraction

 
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