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Ph.D.
(Pharmacy)
DEVELOPMENT AND INVESTIGATION OF NOVEL DRUG ABUSE
DETERRENT TECHNOLOGY FOR TAPENTADOL HYDROCHLORIDE

Ph.D. Scholar : Patel Jayendrakumar Dasharathlal
Research Supervisor : Dr. Rakesh P. Patel

Regi. No.: 19276011003
Abstract :
Background: Increased misuse of pharmaceutical opioid formulation today become one
of the big-socio economical problem for the world and as a part of multidisciplinary
approach, USFDA encourage development and approval of only pharmaceutical opioid
formulation having abuse deterrent characteristics.

Objectives: To develop and in-vitro investigation of novel controlled release anti-overdose
crush and extraction-resistant drug delivery system.

Methods: Drug particulates of Tapentadol HCl was fabricated using different polymers by
thermal and non-thermal manufacturing process. Controlled release properties were
incorporate by applying extended-release coat on the drug particulates to match
dissolution profile with Brand NUCYNTA-ER. Self-regulated pH modulating release
properties was incorporated by addition of pH dependent release and pH elevating
component. The drug particulates composition were optimized by-applying factorial
design. Naltrexone HCl as separate subunits in non-releasable form was incorporated in
the dosage form to hinder tampering with the dosage form.

Results: Only drug particulate made of Polyox retarded drug extraction by >80% at RT
and >90°C. After 5 minutes of grinding in coffee grinder, crushed drug particulates
containing Polyox were retained >99% on the ASTM-170# screen. The
syringeability/injectability attempt was unsuccessful. In normal conditions, Tapentadol
HCl released >90% at 8 hours while no release of Naltrexone HCl. In overdose condition,
none of the Tapentadol HCl and Naltrexone HCl were release at 8 hours. Different in-vitro
manipulation studies indicated that Tapentadol HCl and Naltrexone HCl were
released/extracted simultaneously.

Conclusion: The analytical data demonstrated successful anti-overdose properties of
Tapentadol HCl while hindering crush-and-extraction resistant to the dosage form.
Key words: Abuse, Opioid, Overdose, Tapentadol HCl, Tamper Resistant, Naltrexone HCl,
Extraction

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