(404) Extraction testing of a novel extended-release, abuse-deterrent formulation of morphine, Morphine ARER, in common household solvents
Journal of Pain 2014.01.315
By R Bianchi, E Kinzler, R DiFalco, M Shah, and S Aigner; Inspirion Delivery
Technologies LLC, Valley Cottage, NY
Abusers of prescription opioids commonly extract the active ingredient from
non-abuse deterrent, extended-release formulations to bypass the intended
slow release characteristics and increase the opioid’s bioavailability for injection,
smoking, or oral administration. Abuse deterrent products are designed
to increase the hurdles required to extract the active ingredient with the ultimate
goal of decreasing the misuse and abuse of these formulations for all
routes of administration dependent on extraction. The FDA’s Draft Guidance
for Industry, Abuse-Deterrent Opioids – Evaluation and Labeling (January
2013) recommends that laboratory-based in vitro manipulation and extraction
studies be performed to evaluate the physical characteristics of a novel product
and to guide the downstream pharmacokinetic (PK) and clinical abuse studies.
To assess the abuse deterrent properties of an investigational extended-release
formulation of morphine, Morphine ARER, in vitro laboratory testing was performed
to assess the extractability of morphine. Five intact and five finely
crushed tablets were dissolved in 30 mL of household solvents including water,
saline solution, vinegar, coke, pH 2, pH 4, pH 6, pH 10, 5% ethanol, 10%
ethanol, 20% ethanol, 40% ethanol, and 90oC water. The percent of morphine
released was assessed via liquid chromatography. Morphine ARER did not dose
dump morphine under any condition or solution. Water was found to be the
best solvent for extraction. Interestingly, the amount of morphine released
was largely similar between crushed and intact tablets and reduced in
increasing concentrations of ethanol. These data clearly indicate that
Morphine ARER was highly resistant to extraction and did not result dose
dumping either from intact or ground tablets, even at 30 minutes, which is
longer than an abuser would be expected to wait. Funding Provided by Inspirion
Delivery Technologies LLC.
Can drug design inhibit abuse?
Journal of psychoactive drugs. 2005;37(4):343-362.
By Coleman JJ, Bensinger PB, Gold MS, Smith DE, Bianchi RP, DuPont RL.
A recent federal report indicates that prescription drug abuse is now the second leading category of illicit drug use, following marijuana use. Control strategies typically focus on reducing the diversion of prescription drugs from legitimate sources. The proliferation of unregulated Internet sources, however, has rendered control strategies less effective. This study examines a new approach that focuses on reducing abusability through the use of abuse-resistant drug designs. Drugs with and without such designs are compared and abuse levels assessed using multiple sources. In every instance, drugs employing abuse-resistant designs were found to have significantly lower levels of abuse than comparator drugs without such designs.