(M1230-03-13) A Heat-Shielded Abuse Deterrent Formulation

Purpose: Heat treatment is a strategy by which abusers overcome the viscosity and physical stability of the abuse-deterrent formulation containing poly(ethylene oxide). Therefore, it would be necessary to add thermally-resistant excipients that make the final composition of ADFs much more resistant to crushing after thermal manipulation [1-2]. Silicon dioxide, SiO₂, is composed of silicon and oxygen and it is currently being used in solid dosage forms as an anticaking agent. Although this inorganic compound has multiple applications in pharmaceutical dosage forms, its heat-shielding properties and their potential use in ADFs have not been thoroughly investigated. In this study, we prepared tablets containing PEO and SiO₂ and evaluated the crush-resistant properties of tablets at a higher temperature (180°C), and demonstrated that such tablets can effectively deter abuse by crushing and grinding.

Methods: Tablets were prepared using PEOs with a Mol. Wt. of 100,000 Da and Silicon dioxide (50-70 mesh particle size) or Avicel (control) as a filler. A single station compression press was used to prepare tablets (500 mg) using a direct compression method. The tablets contained 200 mg PEO and 300 mg of Avicel or SiO₂ as a filler. The tablets were heated in an air-circulated oven at 180°C for 1h, and the crush resistance of the heat-treated (HT) tablets was investigated using a ball mill at a full speed of 25 Hz for 5 min. followed by sieve analysis.

Results: The particles were sieved to determine particle size distribution via sieve analysis. The tablets containing SiO₂ demonstrated much more resistance against crushing (Table 1). The percentage of particles ≤250 µm was considered the cut-off point, where they are more appropriate for snorting. As in Figure 1, with the HT PEO tablets containing Avicel as a filler, around 82% of particles were ≤250 and as such is suitable for nasal insufflation [3]. This number was reduced to approximately 23% in HT PEO tablets containing SiO₂ as a filler. The greater crush resistance of HT PEO-SiO₂ tablet is attributed to the high interaction of the polar SiO₂ particles with PEO chains.

Conclusion: As PEOs are sensitive to thermal manipulations, the addition of SiO₂ as an inorganic filler to a PEO-based formulation can contribute to the mechanical and thermal stability of the formulation. We found out that SiO₂ can prevent PEO from thermal oxidation and protect the PEO tablets against thermal manipulation.

References: [1] N.S. Vrandecic, M. Erceg, M. Jakic, I. Klaric, Kinetic analysis of thermal degradation of poly(ethylene glycol) and poly(ethylene oxide)s of different molecular weight, Thermochim Acta, 498 (2010) 71-80.
[2] H. Omidian, N. Babanejad, Detering Abuse of Pharmaceutical Products 2020.
[3] N. Babanejad, U. Kandalam, R. Ahmad, Y. Omidi, H. Omidian, Abuse-deterrent properties and cytotoxicity of poly(ethylene oxide) after thermal tampering, Int J Pharmaceut, 600 (2021).

Acknowledgements:Research reported in this abstract was supported by Nova Southeastern University, HPD Grant with index number of 334601.


Figure 1. The HT LMW PEO tablets were crushed by a ball mill.


Table 1. Particle size distribution of HT 180 PEO-Avicel as well as HT 180 PEO-SiO2 crushed tablets.