Crush resistance and insufflation potential of poly(ethylene oxide)-based abuse deterrent formulations

Muppalaneni, Srinath; Mastropietro, David J; Omidian, Hossein

doi:10.1080/17425247.2016.1211638

Cited by 11 publications

(4 citation statements)

References 8 publications

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“…Application of heat, such as during the printing process, also changes the physical state of PEO, resulting in high mechanical strength, thereby making its use favourable for abuse-deterrence. Thus, it can be concluded that printlets containing PEO are more resistant to abuse through the nasal route when compared to heat-treated PEO tablets previously reported by Muppalaneni et al (Muppalaneni et al, 2016). In vitro dissolution studies show that despite the addition of the PEO, the formulations still retained their alcohol-resistant properties, wherein ƒ2 similarity values of and 84…”

Section: Resultsmentioning

confidence: 49%

3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties

Ong

Awad

Martorana

et al. 2020

International Journal of Pharmaceutics

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In the past decade, prescriptions for opioid medicines have been exponentially increasing, instigating opioid abuse as a global health crisis associated with high morbidity and mortality. In particular, diversion from the intended mode of opioid administration, such as injecting and snorting the opioid, is a major problem that contributes to this epidemic. In light of this, novel formulation strategies are needed to support efforts in reducing the prevalence and risks of opioid abuse. Here, modified release tramadol printlets (3D printed tablets) with alcohol-resistant and abuse-deterrent properties were prepared by direct powder extrusion three-dimensional printing. The printlets were fabricated using two grades of hydroxypropylcellulose (HPC). Both formulations displayed strong alcohol-resistance and had moderate abuse-deterrent properties. Polyethylene oxide (PEO) was subsequently added into the formulations, which improved the printlets' resistance to physical tampering in nasal inhalation tests and delayed their dissolution in solvent extraction tests. Overall, this article reports for the first time the use of direct powder extrusion three-dimensional printing to prepare drug products with both alcohol-resistant and abuse-deterrent properties. These results offer a novel approach for the safe and effective use of opioids that can be combined with the advantages that 3D printing provides in terms of on-demand dose personalisation.

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Section: Resultsmentioning

confidence: 49%

3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties

Ong

Awad

Martorana

et al. 2020

International Journal of Pharmaceutics

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“…A separate study also suggested that method of comminution used had the most prominent effect on tablet fragment size when powerful electric instruments such as high shear grinders are used. 23 Given this, we may conclude that grinding tablet compacts and further sieve analysis may not be the best determinant for such tamper resistant testing. The use of dynamic image analysis to assess the particle size of PEO based tablets crushed using a coffee grinder did show that the biggest factor affecting particle size was the curing temperature; higher curing temperatures and times resulted in more coarse particles.…”

Section: Resultsmentioning

confidence: 99%

“…We considered the percent of fragments greater than 850 µm as an indication of crush resistance by commonly available household comminution practices. 23 We therefore used “% of fragments >850 µm” throughout the paper as an indicator of tablet compact mechanical strength. The higher the percentage of larger particles (>850 µm), the greater is the resistance to crushing, chewing, and grinding.…”

Section: Methodsmentioning

confidence: 99%

Determining Abuse Deterrence Performance of Poly (ethylene oxide) Using a Factorial Design

Joshi¹,

Muppalaneni²,

Omidian³

et al. 2018

Adv Pharm Bull

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Purpose: The purpose of this study was to determine the effects of thermal processing and antioxidant formulation variables on the abuse deterrence performance of a high molecular weight poly(ethylene oxide) (PEO) polymer.Methods: A 24 factorial design with one categorical factor (antioxidant type) and three continuous factors (curing time, curing temperature, % antioxidant) was used. Abuse deterrence performance was evaluated using solution viscosity, surface melting temperature, and mechanical strength. Thermal degradation of PEO powders before compaction was also studied using DSC, FTIR spectroscopy, and viscosity analysis.Results: Our results showed that curing temperature and type of antioxidant can significantly affect the deterrence performance of PEO. The main effect plot for viscosity shows the most prominent factors affecting viscosity are curing temperature and type of antioxidant. However, curvature in the linear model obtained was not sufficient to completely describe the behavior. For surface melting temperature, butylated hydroxytoluene was associated with higher surface melting temperatures compared to ascorbic acid. Additionally, higher percent of antioxidant resulted in higher melting temperature. Particle size distribution to indicate mechanical strength showed no significant effects of tested factors. This suggests that comminution method has more prominent effect on tablet fragment size than the formulation and processing factors studied.Conclusion: While heat confers the mechanical strength to the polymer, it can diminish its physical stability and solution state viscosity. The experimental studies showed that prolonged exposure to high temperatures, even in the presence of antioxidants, can severely hamper polymer deterrence performance in both solid and solution states.

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“…These are common household items used for tampering with prescription opioid medications. For PSR, the intact pellets were hit by a hammer with ten repeated strokes (Muppalaneni et al, 2016). Approximately 5 g of each formulation was weighed, and placed in a motor or coffee blender, and ground for 3 min using a pestle and 1-3 min in the coffee blender.…”

Section: Physical Manipulation and Particle Size Reduction-mentioning

confidence: 99%

Extended release pellets prepared by hot melt extrusion technique for abuse deterrent potential: Category-1 in-vitro evaluation

Butreddy

Sarabu

Dumpa

et al. 2020

International Journal of Pharmaceutics

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The objective of the present study was to develop extended-release (ER) hot-melt extruded (HME) abuse-deterrent pellets of acetaminophen, a model drug, by utilizing high molecular weight polyethylene oxide (PEO) and gelling agents (xanthan gum, guar gum, and gellan gum). The HME pellets were evaluated for their abuse-deterrence (AD) potential by Category-1 laboratory in-vitro evaluation parameters, including particle size reduction (PSR), small volume extraction, dissolution, viscosity, syringeability, and injectability. Further, the pellets were investigated for resistance to physical (crushing) and thermal (oven and microwave) manipulation to evaluate the strength of the AD properties. Physical manipulation studies demonstrated that the pellets were intact, extremely hard, and resistant to PSR and manipulation to bypass ER properties. Dissolution of all intact and physically manipulated pellets led to complete drug release within 8 h, and resistance to dose-dumping in 40% ethanol was observed. The drug extraction was <50% in 10 mL of ingestible and non-ingestible solvents under static, agitation, and thermal manipulation conditions with an incubation time of 30 min. The PEO/xanthan gum-based formulation showed higher viscosity, syringe and injection forces, and lower syringeable volume in all manipulation *

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Crush resistance and insufflation potential of poly(ethylene oxide)-based abuse deterrent formulations

Abstract: Testing methods for crush resistance may not be applicable to all products nor allow control over all process factors. Notwithstanding, the use of high-powered electrical devices may be an effective discriminatory tool for testing heat treated PEO-based ADFs.

Cited by 11 publications

References 8 publications

3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties

3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties

Determining Abuse Deterrence Performance of Poly (ethylene oxide) Using a Factorial Design

Extended release pellets prepared by hot melt extrusion technique for abuse deterrent potential: Category-1 in-vitro evaluation

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