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Evaluation of Abuse-Deterrent Characteristics of Tablets Prepared via Hot-Melt Extrusion

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  • Theme: NIPTE on Current Topics in Abuse Deterrent Science
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Abstract

In this study, the effect of formulation variables and process parameters on the abuse-deterrent (AD) characteristics of a matrix tablet manufactured using hot-melt extrusion (HME) was investigated. The formulation variables included polyethylene oxide (PEO) grades and its input level, while the HME process parameters varied were barrel temperature profile and die diameter. Depending on the diameter of the extrudate (2.5 mm or 5.0 mm), two different downstream processes were used to prepare the tablets: cryo-milling followed by compression for the 2.5 mm extrudate, and cutting followed by compression for the 5.0 mm extrudate. A D-optimal statistical design was used to evaluate the impact of formulation and process parameters on various responses, including tablet physical strength, particle size after manipulation, syringeability and injectability, solution viscosity, extractability in solvents, and dissolution rates. It was found that the post-HME extrusion processing method played a critical role in affecting the AD characteristics of abuse-deterrent formulations, likely through changing the tablet compactability and porosity. When the extrudates were cryo-milled-compressed, the tablets could be readily manipulated by milling, which led to high degree of extractability. Under high alcohol concentration, burst drug release was observed for the tablets compressed from cryo-milled extrudates. Additionally, heat exposure during HME process caused significant drop in PEO solution viscosity, likely due to thermal degradation.

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Authors and Affiliations

  1. Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    Xiaoming Xu, Akhtar Siddiqui, Charudharshini Srinivasan, Adil Mohammad, Ziyaur Rahman, Maxwell Korang-Yeboah, Xin Feng, Mansoor Khan & Muhammad Ashraf

  2. Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, Texas, 77843, USA

    Ziyaur Rahman & Mansoor Khan

Authors
  1. Xiaoming Xu
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  2. Akhtar Siddiqui
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  3. Charudharshini Srinivasan
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  4. Adil Mohammad
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  5. Ziyaur Rahman
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  6. Maxwell Korang-Yeboah
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  7. Xin Feng
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  8. Mansoor Khan
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  9. Muhammad Ashraf
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Correspondence to Muhammad Ashraf.

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Guest Editors: Heather Boyce, Steve R. Byrn, and Stephen W. Hoag

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Xu, X., Siddiqui, A., Srinivasan, C. et al. Evaluation of Abuse-Deterrent Characteristics of Tablets Prepared via Hot-Melt Extrusion. AAPS PharmSciTech 20, 230 (2019). https://doi.org/10.1208/s12249-019-1448-2

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  • DOI: https://doi.org/10.1208/s12249-019-1448-2

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