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

Abstract

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 conditions compared with plain PEO pellets. These findings supported the AD potential of PEO and xanthan gum pellets against intravenous abuse.

Keywords: Abuse-deterrent formulation; Gelling agent; Hot melt extrusion; Physical and thermal manipulation; Polyethylene oxide; Syringeability and Injectability.