Self-regulated Anti-Overdose Crush and Extraction-Resistant Drug Delivery System to Combat Opioid Overdose Crisis

Pharmaceutical opioid dosage forms are commonly misused via an oral route in non-manipulated form, i.e., overdose in intact form, or manipulated form, i.e., after crushing the dosage form, and also via the non-oral route in manipulated form, particularly the parenteral or nasal route. To assess the self-regulated anti-overdose property, crushing strength, extractability, and syringeability of the developed drug delivery system by in vitro laboratory studies. Tapentadol HCl drug particulates fabricated using different polymers were assessed for extractability studies in 25 ml of water at room temperature (RT) and at > 90°C. Crushing strength was assessed by grinding the drug particulates in a mortar and pestle and a coffee grinder for 1 min. For syringeability, an attempt was made to withdraw the drug mixture using a 1 ml insulin syringe for 1 min. To assess the self-regulated anti-overdose property, in vitro dissolution testing on a single-capsule per dissolution vessel (normal condition) and four-capsules per dissolution vessel (overdose condition) was performed. POLYOX, Natrosol, and Blanose-containing drug particles retarded drug extraction by > 80% at RT and > 90°C. After 1 min of grinding in a mortar and pestle and a coffee grinder, crushed POLYOX-containing drug particulates were retained at > 99% on the ASTM-170# screen. The attempt to withdraw the viscous mixture of drug formulation prepared with 5 ml of water for 1 min using a 1 ml insulin syringe was unsuccessful. In dissolution studies, more than 90% of the drug was released in normal conditions, and more than 90% of the drug was retarded in overdose conditions. In vitro laboratory studies demonstrate that the developed self-regulated anti-overdose crush-resistant drug delivery system may deter misuse via oral and non-oral routes.

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Jayendrakumar, P., Rakesh, P. Self-regulated Anti-Overdose Crush and Extraction-Resistant Drug Delivery System to Combat Opioid Overdose Crisis. AAPS PharmSciTech 23, 265 (2022). https://doi.org/10.1208/s12249-022-02423-5