Abuse-deterrent features of an extended-release morphine drug product developed using a novel injection-molding technology for oral drug delivery.

Objective: A novel technology platform (Guardian™ Technology, Egalet Corporation, Wayne, PA) was used to manufacture morphine abuse-deterrent (AD), extended-release (ER), injection-molded tablets (morphine-ADER-IMT; ARYMO® ER [morphine sulfate] ER tablets; Egalet Corporation), a recently approved morphine product with AD labeling. The aim of this article is to highlight how the features of Guardian™ Technology are linked to the ER profile and AD characteristics of morphine-ADER-IMT.

Results: The ER profile of morphine-ADER-IMT is attributed to the precise release of morphine from the polymer matrix.

Clinical relevance of the pharmacokinetic characteristics of an abuse-deterrent, extended-release, injection-molded morphine tablet.

Objective: To characterize the pharmacokinetics (PK) and in vitro alcohol dissolution characteristics of extended-release (ER), injection-molded (IM) morphine tablets with abuse-deterrent (AD) features (morphine-ADER-IMT).

Design: In vivo, in vitro, and in silico studies were conducted. A randomized, two-cohort study evaluated the bioequivalence of morphine-ADER-IMT (60 mg) to morphine ER (60 mg; MS Contin®; Purdue Pharma LP, Stamford, CT) and characterized the effect of food on the PK profile of morphine-ADER-IMT.

The ALERRT instrument: a quantitative measure of the effort required to compromise prescription opioid abuse-deterrent tablets.

Background: US FDA guidance recommends measuring the degree of effort needed to manipulate abuse-deterrent (AD) opioids. The ALERRT instrument (PinneyAssociates; Bethesda, MD) uses visual analog scales to assess the labor, effort, and resources necessary to physically compromise AD product candidates in standardized settings.

Objective: Use the ALERRT instrument for testing morphine abuse-deterrent, extended-release, injection-molded tablets (ADER-IMT) 60 and 100 mg and the comparators immediate-release (IR) morphine sulfate 30 mg and extended-release (ER) morphine sulfate 60 mg.

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

Objective: To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets.

Methods: A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion.

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) versus Extended-Release Morphine Administered Orally in Nondependent Recreational Opioid Users.

Objective: To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets.

Methods: This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days.

Sodium glycocholate transport across Caco-2 cell monolayers, and the enhancement of mannitol transport relative to transepithelial electrical resistance.

Ideally, the amount of enhancer remaining at the donor side during an in vitro transport study should be known, in order to know the true enhancer concentration during a permeability study. The purpose of the present study is to estimate the flux of the enhancer, sodium glycocholate (GC), through Caco-2 cell monolayers, and to study the effect of various enhancer concentrations on the permeability of GC itself, the permeability of mannitol and the transepithelial electrical resistance (TEER). Apical to basolateral permeability was measured with various concentrations 0.

Intranasal bioavailability of diazepam in sheep correlated to rabbit and man.

The purposes of the present study were to estimate the nasal bioavailability of diazepam in sheep and to compare this to earlier results in rabbits and humans. Additional, to compare the absorption during various initial periods in the two animal models and man, due to the importance of early absorption in emergency treatment. In a cross-over design, diazepam was nasally administered (7 mg) and intravenously (3 mg), respectively, to six sheep.