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Effect of Manufacturing Process on the Retention of Abuse-Deterrent Properties of PEO-Matrix Tablets

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Abstract

Polyethylene oxide (PEO) is a widely used polymer in the development of abuse-deterrent oral formulations. Different manufacturing processes including direct compression (DC) followed by sintering, wet granulation (WG) followed by compression and sintering, and hot melt extrusion (HME) can be used to manufacture abuse-deterrent oral drug products. Three different manufacturing processes (DC, WG, HME) were evaluated to test the retention of their abuse-deterrent features following attempts to grind the tablets or extrudates. In vitro drug release studies were conducted on 10% and 32% drug-loaded tablets/extrudates prepared using these manufacturing methods, and the release profiles from all formulations showed good extended-release properties. Drug content analysis on the granules obtained from tablets prepared by direct compression showed non-uniform drug distribution where an unexpectedly high drug content was present in the smallest size (< 250 µm) granules, sizes which are likely to be inhaled by abusers. Granules from tablets prepared by wet granulation showed improved drug distribution across all granule sizes formed after grinding. Drug content testing on the granules obtained from extrudates prepared using hot melt extrusion showed excellent drug content uniformity along with sufficient strength to resist grinding into smaller particles. The retention of the abuse-deterrent properties of a dosage form following attempts to extract or abuse the drug is an important product characteristic, and the product design, formulation components, and manufacturing processes can all play critical roles in the retention of the desired abuse-deterrent properties.

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Author information

Author notes

  1. Saikishore Meruva

    Present address: Oral Product Development, Bristol Myers Squibb, New Brunswick, New Jersey, 08901, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, 115 S Grand Avenue, Iowa City, Iowa, 52242-1112, USA

    Leyla Rezaei, Saikishore Meruva & Maureen D. Donovan

Authors
  1. Leyla Rezaei
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  2. Saikishore Meruva
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  3. Maureen D. Donovan
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Contributions

All of the authors participated in the writing and editing of this manuscript. L.R. was responsible for experimental execution and data analysis. S.M. was involved in conceptualization of the studies, experimental design, and data analysis. M.D.D. was responsible for conceptualization of the studies, overall direction of the research, and communication of the results.

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Correspondence to Maureen D. Donovan.

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Rezaei, L., Meruva, S. & Donovan, M.D. Effect of Manufacturing Process on the Retention of Abuse-Deterrent Properties of PEO-Matrix Tablets. AAPS PharmSciTech 23, 38 (2022). https://doi.org/10.1208/s12249-021-02169-6

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