Abuse-Deterrent Opioid Formulations: Purpose, Practicality, and Paradigms
Jeffrey Fudin, BS, PharmD, DAAPM, FCCP
When reflecting on commonly abused drugs, pharmacists generally focus attention on cocaine, amphetamines and methylphenidate, barbiturates, hallucinogens such as ketamine (“Special K”), benzodiazepines, marijuana, and designer drugs such as “bath salts.” However, the standouts these days seem to be heroin and prescription opioids.
According to the National Institute on Drug Abuse, the number of deaths from prescription opioid analgesics has sky rocketed from 2001 to 2011, accounting for a 4-fold increase in the total number of deaths from opioids and creating what many claim to be an “opioid epidemic.” In 2013, the US Centers for Disease Control and Prevention (CDC) revealed that opioid analgesics including Vicodin and OxyContin caused 75% of prescription drug overdoses, outpacing both cocaine and heroin overdoses combined. The most up-to-date data is posted on the CDC’s Prescription Drug Overdose in the United States: Fact Sheet.
While extended-release (ER) opioid analgesics are an essential component of pain management, abuse and misuse of these medications can cause substantial morbidity and mortality. Abusers often manipulate ER opioid formulations by crushing, chewing, snorting, vaping, or injecting the total dose. Drug seekers are particularly interested in the ER formulations because tampering with these products provides them with a higher maximum concentration of the drug in a small volume of powder, which is easily snorted with minimal discomfort compared to the large amount of powder (and excipients) required of standard immediate-release (IR) dosage formulations.
For this reason, at least in part, lawmakers and the FDA have assigned blame to ER formulations for the opioid epidemic and increased mortality from overdose. Without a doubt, the fire was disproportionately fueled when the FDA approved Zohydro ER, a prescription single-entity hydrocodone ER medication. Zohydro ER uses a Spheroidal Oral Drug Absorption System (SODAS), which is not an abuse-deterrent formulation (ADF). Once ingested, the hard gelatin layer dissolves and gastrointestinal fluid enters the beads. The active medication then diffuses out of the beads, allowing both immediate and time release of hydrocodone.
There have been several legislative attempts to combat the opioid epidemic over the years. For instance, Congressmen Bill Keating (D-MA) introduced the Stop the Tampering of Prescription Pills (STOPP) Act to address opioid abuse and misuse. The STOPP Act was the first federal legislation that directed pharmaceutical manufacturers to invest in research and production to create ADFs of opioids.
Subsequently, the FDA has tried to combat the epidemic by creating more stringent regulations regarding approval of opioid formulations. In fact, the FDA is moving towards a requirement for all future formulations of ER opioids to contain abuse-deterrent properties.
ADFs are designed to obviate tablet or capsule manipulation for dose dumping orally, crushing and/or dissolving for injection, or snorting. Various designs for ADFs have been suggested, including physical/chemical barriers, agonist/antagonist combinations, aversion properties, altered release design, or a prodrug formulation of the medication.
There are numerous opioids that have abuse-deterrent properties but have not been approved by the FDA as an ADF. These include Exalgo (hydromorphone), Nucynta ER (tapentadol), Opana ER (oxymorphone), Oxecta (oxycodone), and Xartemis (oxycodone and acetaminophen).
Nucynta ER has properties that make it difficult to crush, cut, or break. Exalgo is available in an Osmotic [Controlled] Release Oral [Delivery] System (OROS) tablet, a dosage form that renders it relatively crush resistant, allowing gradual release of the hydromorphone when used as directed. Oxecta possess 2 unique abuse deterrent properties, as its formulation contains sodium lauryl sulfate, which makes snorting the medication unpleasant, and an excipient that causes the tablet to form a gel if any attempts are made to dissolve it. Similarly, when Opana tablets are crushed, they turn into a gel that is difficult to inject.
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Source: https://www.pharmacytimes.com/view/abuse-deterrent-opioid-formulations-purpose-practicality-and-paradigms