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Physical Barrier Type Abuse-Deterrent Formulations: Mechanistic Understanding of Sintering-Induced Microstructural Changes in Polyethylene Oxide Placebo Tablets

Authors
  • Boyce, Heather J.1
  • Dave, Vivek S.2
  • Scoggins, Myke3
  • Gurvich, Vadim J.4, 5
  • Smith, Daniel T.6
  • Byrn, Stephen R.5, 6
  • Hoag, Stephen W.1, 5
  • 1 University of Maryland, 20 N. Pine St., Baltimore, Maryland, 21201, USA , Baltimore (United States)
  • 2 St John Fisher College, Rochester, New York, NY, USA , New York (United States)
  • 3 Recro Gainesville LLC, Gainesville, Georgia, USA , Gainesville (United States)
  • 4 University of Minnesota, 717 Delaware St. SE, Minneapolis, Minnesota, 55414, USA , Minneapolis (United States)
  • 5 National Institute for Pharmaceutical Technology and Education, 717 Delaware St. SE, Suite 482, Minneapolis, Minnesota, 55414, USA , Minneapolis (United States)
  • 6 Purdue University, West Lafayette, Indiana, USA , Indiana (United States)
Type
Published Article
Journal
AAPS PharmSciTech
Publisher
American Association of Pharmaceutical Scientists
Publication Date
Jan 29, 2020
Volume
21
Issue
3
Identifiers
DOI: 10.1208/s12249-019-1594-6
Source
Springer Nature
Keywords
License
Yellow

Abstract

The main goal of the presented work was to understand changes in the microstructure of tablets, as well as the properties of its main component viz. polyethylene oxide (PEO) as a function of sintering. Key polymer variables and sintering conditions were investigated, and sintering-induced increase in tablet tensile strength was evaluated. For the current study, binary-component placebo tablets comprised of varying ratios of PEO and anhydrous dibasic calcium phosphate (DCP) were prepared at two levels of tablet solid fraction. The prepared tablets were sintered in an oven at 80°C at different time points ranging from 10 to 900 min and were evaluated for pore size, tablet expansion (%), and PEO crystallinity. The results showed that for efficient sintering and a significant increase in the tablet tensile strength, a minimum of 50% w/w PEO was required. Moreover, all microstructural changes in tablets were found to occur within 60 min of sintering, with no significant changes occurring thereafter. Sintering also resulted in a decrease in PEO crystallinity, causing changes in polymer ductility. These changes in PEO ductility resulted in tablets with higher tensile strength. Formulation variables such as PEO level and PEO particle size distribution were found to be important influencers of the sintering process. Additionally, tablets with high initial solid fraction and sintering duration of 60 min were found to be optimal conditions for efficient sintering of PEO-based compacts. Finally, prolonged sintering times were not found to provide any additional benefits in terms of abuse-deterrent properties.

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