In Vitro Assessment of Nasal Insufflation of Comminuted Drug Products Designed as Abuse Deterrent Using the Vertical Diffusion Cell
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In vitro evaluation of abuse deterrent formulations (ADFs) is a challenge since real abuse situations are variable and ADF technology is evolving. Specifically, an assessment of an ADF to deter nasal insufflation would be valuable. In this study, a vertical diffusion cell (VDC) was used to evaluate polyethylene oxide (PEO)-based tablets manipulated by three different forces. The commercially available products Oxycontin®, an ADF, Opana®, and metoprolol tartrate tablet formulations made in our laboratory were studied. Particle size distribution and percent recovery of manipulated tablets were measured. Grinding produced the lowest recovery and the smallest particle size distribution. Drug release was examined using a VDC by placing the dry comminuted particles on an enclosed wetted cellulose membrane. Dispensing dry particles on a VDC is atypical but includes some key features associated with an abuse situation where once the particles are snorted, the moisture in the nasal mucosa activates hydration and swelling of the polymers in the formulation, retarding drug release. Drug release from OxyContin®, Opana®, and metoprolol tablets were analyzed for the cutting, grinding, and milling modes of abuse. The analysis showed that in most cases, the mode of abuse produced different particle sizes with different release rates. Statistically different release rates were observed for metoprolol tablets made with different molecular weight PEO and with different porosities. These results indicate that within detection limits, the VDC can be used to quantitate release differences due to various modes of abuse used in this study.
KEY WORDSabuse deterrent formulations (ADFs) oxycontin® Opana® ER vertical diffusion cell (VDC) polyethylene oxide (PEO)
The authors would like to acknowledge Hanson Research Corporation for the generous use of equipment to conduct the diffusion studies; Dow Chemical for their donation of various POLYOX grades; Noramco for their donation of oxycodone HCl and oxymorphone HCl reference material. The authors would also like to acknowledge PhRMA foundation, the National Institute for Pharmaceutical Technology and Education (NIPTE), and the US Food and Drug Administration (FDA) for providing funds for this research. This study was funded by the FDA GDUFA contract to NIPTE (# HHSF223201301189P). This work was submitted in partial fulfillment of Ph.D requirement for Heather Boyce.
Compliance with Ethical Standards
Views expressed in this publication do not necessarily reflect the official policies of the FDA, nor does any mention of trade names, commercial practices, or organization imply endorsement by the FDA.
This paper was written in partial fulfillment of a Ph.D. thesis.
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