title: Risk based in vitro performance assessment of extended release abuse deterrent formulations.
abstract: High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products.
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Abhay
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Manar
authors.initials: M
authors.lastname: Al-Ghabeish
authors.affiliation: Controlled Substance Staff, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Silvia N
authors.initials: SN
authors.lastname: Calderon
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA; Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, College Station, TX 77843, USA. Electronic address: mkhan@pharmacy.tamhsc.edu.
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000701:Analgesics, Opioid / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004333:Drug Administration Routes; D004339:Drug Compounding; D006801:Humans; D012306:Risk; D013015:Sotalol / Q000737:chemistry; D019966:Substance-Related Disorders / Q000517:prevention & control*
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D013015:Sotalol
keywords: Abuse deterrent formulation; Drug abuse; Evaluation matrix; Injectability; Mode of abuse; Opioid analgesics; Syringeability; manipulation