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Int J Pharm ; 600: 120481, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766634


Poly(ethylene oxide) (PEO) is the most common deterring agent used in the abuse-deterrent formulations (ADFs). In this study, we investigated the PEO's abuse-deterrent properties and its potential cytotoxicity after being heated at high temperatures (80 °C and 180 °C). The results indicated a significant loss in both crush and extraction resistance features of the polymer, which is primarily associated with the polymer degradation at the higher temperatures. The heat-treated PEO at the high temperature was also found to lose its controlled-release feature, upon which over 80% of the drug was released after one hour in the simulated gastric fluid. The cytotoxicity of the PEO was further assessed to evaluate the safety of the polymer following the thermal treatment. Our findings revealed a substantial loss in the viability of the cells exposed to the PEO treated at higher temperatures. Taken all, heating PEO at high temperatures can lead to a significant loss in both the crush/extraction resistance characteristics and the safety of the polymer. These findings reemphasize the fact that more appropriate and stricter test and regulations will be needed to assure that the abuse deterrent formulations are safe and effective under severe conditions of abuse.

Int J Pharm ; 577: 119042, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31953084


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.

Formulações de Dissuasão de Abuso/métodos , Analgésicos Opioides/administração & dosagem , Carboximetilcelulose Sódica/química , Analgésicos Opioides/química , Química Farmacêutica , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Concentração Osmolar , Solventes/química , Abuso de Substâncias por Via Intravenosa/prevenção & controle
Int J Pharm ; 569: 118602, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394182


An innovative abuse-deterrent composition was developed to deter the most dangerous route of drug abuse, the intravenous route. The composition is based on a crosslinked sodium starch glycolate (X-SSG) that can effectively complex with cationic drugs in aqueous solutions and minimize the amount of the free drug available for extraction. Furthermore, the crosslinked polymer swells in and entraps a portion of the drug solution by which it reduces the available volume for syringing and subsequent injection. Two deterrent compositions were prepared, a drug-polymer physical blend and a drug-polymer chemical complex. The composition in its complexed form showed greater deterrence capacity than the physical blend except in solvents with ionic moieties, where the deterrence remained almost the same. The studies revealed that the complexation with the drug played a major role in total drug entrapment. Tablets prepared from the drug-polymer complex showed a complete and immediate drug release in 0.1 N HCl within the first 15 min. Moreover, the dissolution studies in the simulated intestinal media ruled out the re-complexation potential between the drug and the polymer. The proposed X-SSG composition provides a desirable drug release in the gastric and intestinal media under the legitimate use while deterring an intravenous abuse.

Formulações de Dissuasão de Abuso , Amido/análogos & derivados , Liberação Controlada de Fármacos , Suco Gástrico/química , Secreções Intestinais/química , Amido/química , Comprimidos
Expert Opin Drug Metab Toxicol ; 14(12): 1255-1271, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30408424


INTRODUCTION: Prescription opioid abuse is now an epidemic that has forced the government and industries to take initiatives. These include developing abuse-deterrent formulations (ADFs), issuing regulatory guidances and allocating massive budgets to ensure the safety and effectiveness of these medications. Areas covered: This review covers the regulatory guidance on evaluation and labeling of the branded and generic ADFs. It also includes the relevant patents and technologies, the in-vitro, in-vivo, the post-marketing data, the FDA reviews, and the products' labeling of the FDA-approved products with abuse-deterrent features. Expert opinion: Despite the development of a dozen products with abuse-deterrent features, most of these technologies rely on the same deterrent agent, making it easier for abusers to focus their manipulation efforts and share their experience to defeat the technology. Further advancement in the field requires developing more robust, more diverse, safer, and affordable deterrent technologies for the extended- and immediate-release opioid products. Moreover, advances in the reporting of the post-market results, issuance of policies in support of the ADFs, and concurrent monitoring of the illicit opioid market are other considerations that can further help in confronting the epidemic.

Formulações de Dissuasão de Abuso , Analgésicos Opioides/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Analgésicos Opioides/efeitos adversos , Desenho de Fármacos , Rotulagem de Medicamentos , Humanos , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Estados Unidos , United States Food and Drug Administration