Abstract

SELF-REGULATED ANTI-OVERDOSE CRUSH-RESISTANT DRUG DELIVERY SYSTEM DESIGNED TO ADDRESS THE OPIOID ABUSE CRISIS

Pravinkumar Darji*, Jayendrakumar Patel, Rakesh Patel, Binit Patel, Viratkumar Khatri, Praneeth Ivan Joel Fnu and Seshadri Nalla

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Abstract

Background: The pharmaceutical opioid dosage form is frequently misused through the oral route, either in its original form by taking an excessive dose, or in a manipulated form by crushing the dosage form. It can also be misused through non-oral routes, particularly through injection or nasal administration, after manipulating the dosage form. Objectives: The objective is to evaluate the self-regulated antioverdose characteristics of the crush-resistant drug delivery system by conducting in-vitro laboratory research on its crushing strength, extractability, and syringeability. Methods: The extractability of Metformin HCl drug particles, produced using various polymers, was evaluated in 25ml of water at room temperature (RT) and at temperatures exceeding 90°C. The assessment of crushing strength involved grinding the drug particles using a mortar-pestle and a coffee grinder for a duration of 1 minute. In order to assess the syringeability of the drug mixture, an effort was made to extract it using a 1ml Insulin syringe for a period of 1 minute. In order to evaluate the ability of self-regulation against overdose in both normal and overdose scenarios, we conducted in-vitro dissolving testing. This involved evaluating a single, unaltered capsule per dissolution vessel for normal settings, and four capsules per dissolution vessel for overdose situations. Results: The presence of drug particles comprising polyox, natrosol, and blanose significantly reduced the extraction of the drug by more than 80% at room temperature and over 90°C. After grinding in a mortar-pestle and a coffee grinder for 1 minute, the crushed particles of thermally produced drug particulates containing polyox were able to be retained at a rate of over 99% on the ASTM 170# screen. The endeavor to extract the thick and sticky combination of drug formulation, which was mixed with 5ml of water, using a 1ml insulin syringe for a duration of 1 minute, did not succeed. During the dissolution trial, unaltered capsules exhibited a drug release of over 90% and significantly slowed down drug release by over 90% under normal and overdose circumstances, respectively. Conclusion: Laboratory experiments conducted in a controlled environment show that the newly created drug delivery system, which is designed to prevent overdosing and resist crushing, has the potential to discourage abuse through both oral and non-oral methods of administration.

Keywords: Abuse Deterrent, Over Dose Abuse, Tamper Resistant, Opioid, Chronic Pain, Metformin HCl, Extraction, Syringeability, Crushing.