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A Chewing Study of Abuse-Deterrent Tablets Containing Polyethylene Oxide Using a Robotic Simulator

  • Research Article
  • Advancements in Modified-release Oral Drug Delivery - Delivery throughout the Gastro-intestinal Tract
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Abstract

Abuse-deterrent formulations (ADFs) refer to formulation technologies aiming to deter the abuse of prescription drugs by making the dosage forms difficult to manipulate or extract the opioids. Assessments are required to evaluate the performance of the drugs through different routes including injection, ingestion, and insufflation and also when the drugs are manipulated. Chewing is the easiest and most convenient way to manipulate the drugs and deserves investigation. Chewing is one of the most complex bioprocesses, where the ingested materials are subject to periodic tooth crushing, mixed through the tongue, and lubricated and softened by the saliva. Inter- and intra-subject variations in chewing patterns may result in different chewing performances. The purpose of this study is to use a chewing simulator to assess the deterrent properties of tablets made of polyethylene oxide (PEO). The simulator can mimic human molar grinding with variable chewing parameters including molar trajectory, chewing frequency, and saliva flow rate. To investigate the effects of these parameters, the sizes of the chewed tablet particles and the chewing force were measured to evaluate the chewing performance. Thirty-four out of forty tablets were broken into pieces. The results suggested that the simulator can chew the tablets into smaller particles and that the molar trajectory and saliva flow rate had significant effect on reducing the size of the particles by analysis of variance (ANOVA) while the effect of chewing frequency was not clear. Additionally, chewing force can work as an indicator of the chewing performance.

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Acknowledgements

The authors would like to thank Associate Professor Meng Wai Woo from the Department of Chemical and Materials Engineering, the University of Auckland, for his assistance on testing the tablet strengths.

Funding

The authors would like to acknowledge the US Food and Drug Administration (FDA) for the providing financial support for this research under FDA contract 75F40121C00178.

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Authors and Affiliations

  1. Department of Mechanical and Mechatronics Engineering, The University of Auckland, 5 Grafton Rd, Auckland, 1010, New Zealand

    Bangxiang Chen, Jaspreet Dhupia & Weiliang Xu

  2. College of Pharmacy, The University of Texas at Austin, 107 W. Dean Keeton St., Austin, Texas, 78712, USA

    Feng Zhang & Mark Costello

  3. Food Materials & Structures, Plant & Food Research Ltd, 74 Gerald Street, Lincoln, 7608, New Zealand

    Marco P. Morgenstern

  4. Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    Heather Boyce, Wei-Jhe Sun & Saeid Raofi

  5. Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20705, USA

    Li Tian

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  1. Bangxiang Chen
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Contributions

All of the authors participated in the writing and editing of this manuscript. B.C. was responsible for experimental execution and data analysis. J.D., F.Z., M.M., and W.X. were involved with the conceptualization of the studies. M.C. and F.Z. were responsible for preparing the materials used in the study.

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Correspondence to Bangxiang Chen.

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Chen, B., Zhang, F., Dhupia, J. et al. A Chewing Study of Abuse-Deterrent Tablets Containing Polyethylene Oxide Using a Robotic Simulator. AAPS PharmSciTech 24, 245 (2023). https://doi.org/10.1208/s12249-023-02706-5

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