Development and impact of prescription opioid abuse deterrent formulation technologies.

BACKGROUND: Millions of patients are treated with opioid analgesics (OpAs) to relieve pain. Unfortunately, these medications are subject to abuse and/or unintended misuse. Abuse deterrent formulations (ADFs) represent an intervention strategy to decrease abuse/misuse without affecting patient access. The Food and Drug Administration (FDA) has issued Draft Guidance "Abuse deterrent opioids, Evaluation and Labeling" and is currently actively pursuing scientific input on this issue. METHODS: The development of ADF technologies was reviewed using peer reviewed journals describing OpA post marketing studies, web sites containing FDA announcements on product approvals and manufacturer product use profiles. RESULTS: Reviewed is the FDA recent approval of a product label describing the abuse deterrent characteristics of OxyContin(®) (physical barrier formulation), and the FDA determination that studies were insufficient for an Opana(®) (physical barrier) ADF label. Additional reviewed marketed OpAs with ADF technologies include: Suboxone(®) and Embeda(®) (opioid agonist/antagonist combinations), Oxecta(®) (aversion technology), and Nucynta(®) (physical barrier). Reviewed ADF technologies currently in development include: new physical barrier and aversion technologies, an innovative extended release formulation as well as novel polymer-opioid conjugates. As ADF technologies are part of a comprehensive intervention strategy to promote safe OpA use, additional components including governmental, community, and educational initiatives are reviewed. CONCLUSIONS: The outcomes of the recent ADF labeling applications for OxyContin(®) (Tier 3 approval) and Opana(®) (non-approval) suggest that the threshold for ADF labeling will be appropriately high. The presented findings indicate that ADF technologies can be a critical component of a comprehensive strategy to promote the safe and effective use of OpAs.

An iterative model for in vitro laboratory assessment of tamper deterrent formulations.

BACKGROUND: In an effort to address the continuing problem of prescription opioid abuse, manufacturers are incorporating new technologies into formulations that are designed to deter product tampering and misuse. Standards for laboratory assessment of tamper deterrent properties of new formulations have not previously been developed. METHODS: Experimental designs were developed for the in vitro laboratory assessment of the tamper deterrent properties of reformulated oxycodone. Given that an exhaustive study of all potential tampering methods was impractical; this model was developed to evaluate the product in an incremental fashion with iterative changes that were amenable to objective and replicable laboratory testing. RESULTS: A description of the model is provided along with pertinent examples involving assessment of reformulated oxycodone with comparisons to the original formulation. Physical and chemical procedures were developed that relate to "real-world" scenarios that may be applied to opioid formulations. Test results were interpreted in relation to the relative ease or difficulty of the manipulation as compared to control materials and the amount and purity of active drug that could be accessed. Results from some of the tests were designed to be useful in predicting whether specific tampering methods would facilitate or deter drug administration by different routes of administration. CONCLUSIONS: This model, developed to assess the tamper deterrent properties of reformulated oxycodone, should have application in the assessment of other drug formulations designed to exhibit tamper deterrence properties.