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

Nikolaj Skak, MS; Torben Elhauge, MSc; Jeffrey M. Dayno, MD; Karsten Lindhardt, MSc, PhD, DBE

doi:10.5055/jom.2017.0406

Authors

Nikolaj Skak, MS
Torben Elhauge, MSc
Jeffrey M. Dayno, MD
Karsten Lindhardt, MSc, PhD, DBE

DOI:

https://doi.org/10.5055/jom.2017.0406

Keywords:

abuse-deterrent, extended-release, Guardian™ Technology, injection molding, morphine, physical/chemical barrier

Abstract

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. The approved dosage strengths of morphine-ADER-IMT are bioequivalent to corresponding dosage strengths of morphine ER (MS Contin®; Purdue Pharma LP, Stamford, CT). Morphine-ADER-IMT was very resistant to physical manipulations intended to reduce particle size, with <10 percent of particles being reduced to <500 μm, regarded by the US Food and Drug Administration as a relevant cutoff for potential insufflation in their generic solid oral AD opioid guidance. Furthermore, morphine was not readily extracted from the polymer matrix of morphine-ADER-IMT in small- or large-volume solvent extraction studies that evaluated the potential for intravenous and oral abuse.

Conclusions: The ER profile and AD characteristics of morphine-ADER-IMT are a result of Guardian™ Technology. The combination of the polyethylene oxide matrix and the use of injection molding differentiate morphine-ADER-IMT from other approved AD opioids that deter abuse using physical and chemical barriers. The high degree of flexibility of the Guardian™ Technology enables the development of products that can be tailored to almost any desired release profile; as such, it is a technology platform that may be useful for the development of a wide range of pharmaceutical products.

Author Biographies

Nikolaj Skak, MS

Senior Director, Pharmaceutical Development, Egalet Corporation, Wayne, Pennsylvania

Torben Elhauge, MSc

Senior Scientist Specialist, Research and Development, Egalet Corporation, Wayne, Pennsylvania

Jeffrey M. Dayno, MD

Chief Medical Officer, Egalet Corporation, Wayne, Pennsylvania

Karsten Lindhardt, MSc, PhD, DBE

Senior Vice President, Research and Development, Egalet Corporation, Wayne, Pennsylvania

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