(404) Extraction testing of a novel extended-release, abuse-deterrent formulation of morphine, Morphine ARER, in common household solvents

Abstract

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 The FDA’s Draft Guidance for Industry, Abuse-Deterrent Opioids – Evaluation and Labeling (January 2013) recommends that laboratory-based in vitro manipulation and extraction studies be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.