Abstract
Prescription opioids have widely been abused as an epidemic. In this research, we developed a drug composition based on the crosslinked carboxymethylcellulose (XCMC) and a drug model that can effectively deter abuse by injection via multiple mechanisms. The anionic nature of the XCMC is responsible for complexing the cationic opioids in aqueous solutions, minimizing the free drug amount accessible for extraction. The crosslinked nature of the polymer is responsible for its swelling and partial containment of the drug solution within the swollen polymer’s network, thus minimizing the available volume for subsequent injection. We have shown that XCMC can efficiently interact with cationic drugs in the form of physical blends and chemical complexes in different aqueous solvents, forming abuse-deterrent complexes. The complexation efficiency was affected by the solution pH and ionic strength, as well as the drug to polymer ratio in the formulation. The in vitro dissolution studies were conducted in two stages, the stage I in 0.1 M HCl and the stage II in water and pH 7.5 phosphate buffer. These studies confirmed the proper drug release under the legitimate conditions of use. Therefore, the XCMC polymers have a great potential to be used as deterring agents in developing opioid medications with abuse-deterrent properties.
| Original language | English |
|---|---|
| Article number | 119042 |
| Pages (from-to) | 119042 |
| Journal | International journal of pharmaceutics |
| Volume | 577 |
| DOIs | |
| State | Published - Mar 15 2020 |
Bibliographical note
Copyright © 2020 Elsevier B.V. All rights reserved.Funding
This study was funded by Nova Southeastern University [HPD grant number 335081, 2017]. The funding institution did not contribute to the experimental design and data generation, data analysis, data interpretation, write up, or decision to submit the article for publication.
ASJC Scopus Subject Areas
- Pharmaceutical Science
Keywords
- Abuse deterrent
- Carboxymethylcellulose
- Complex
- Crosslinking
- Opioid abuse
- Swelling
- Opioid-Related Disorders/prevention & control
- Solvents/chemistry
- Chemistry, Pharmaceutical
- Abuse-Deterrent Formulations/methods
- Osmolar Concentration
- Drug Liberation
- Substance Abuse, Intravenous/prevention & control
- Analgesics, Opioid/administration & dosage
- Carboxymethylcellulose Sodium/chemistry
- Hydrogen-Ion Concentration
Disciplines
- Pharmacy and Pharmaceutical Sciences
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