Student Theses, Dissertations and Capstones

Document Type

Dissertation - NSU Access Only

Degree Name

Doctor of Philosophy (PhD) in Pharmacy

First Advisor

Hamid Omidian

Defense Date

1-1-2023

Abstract

The ongoing prescription opioid abuse is a serious problem nationwide. To combat this crisis, abuse-deterrent formulations (ADFs) have been developed utilizing technologies that impede drug manipulation and administration other than intended. Most approved ADFs rely on the same technology and deterring agent and target mostly extended-release products, making immediate-release ones prone to abuse. Moreover, abusers have found unconventional methods to tamper with such formulations. Our comprehensive analyses of poly(ethylene oxide) (PEO) indicate that heating, salts, alcohol, microwaving, crushing under cryogenic conditions, and agitating its solutions can significantly deteriorate the structure of PEO and hence its abuse-deterrent properties. To overcome PEO’s shortcoming in deterring abuse by injection and insufflation, this research will disclose developing an organic-inorganic cryogel composite wherein its organic and inorganic components offer improved crush and extraction resistance, respectively. The developed abuse-deterrent compositions were thoroughly evaluated for their drug entrapment efficiency under different drug abuse conditions. The polymers were considered physical blends with the drug, pre-formed drug-inorganic complexes, and a polymeric hybrid blend with the drug. The drug release from such compositions was also assessed under a simulated gastric medium. Pharmaceutical dosage forms based on the cryogel composite of this study displayed improved crush resistance and extraction resistance compared to their PEO counterparts. The studies showed that complexation is the major contributor to total drug entrapment and that drug-inorganic complexes effectively hindered drug extraction similar to their physical blend counterparts. The organic component of the composite offered crush resistance due to its inherently rubbery and touchy structure, and the inorganic component offered extraction resistance due to its powerful binding to an abusable drug in various extracting solutions. The studies also showed that the most challenging abuse condition was using alcoholic solvents for drug extraction, where electrostatic interferences disturbed the drug-polymer complexation. Therefore, higher free drug amounts could be recovered for abuse. The in vitro drug release studies revealed a complete and sustained drug release for the cryogel composite in simulated gastric fluid. The compositions developed in this research are safe, effective, and robust and can be incorporated to design extended-release drug products, providing considerable intervention to the prescription opioids epidemic.

Subject Categories

Pharmacy and Pharmaceutical Sciences

Keywords

Composite; Cryogel; Opioid Abuse

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