Your browser doesn't support javascript.
loading
Assessing Abuse-Deterrent formulations utilizing Ion-Exchange resin complexation processed via Twin-Screw granulation for improved safety and effectiveness.
Ram Munnangi, Siva; Narala, Nagarjuna; Lakkala, Preethi; Kumar Vemula, Sateesh; Repka, Michael.
Afiliación
  • Ram Munnangi S; Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, USA.
  • Narala N; Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677.
  • Lakkala P; Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677.
  • Kumar Vemula S; Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677.
  • Repka M; Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, USA. Electronic address: marepka@olemiss.edu.
Eur J Pharm Biopharm ; 197: 114230, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38373555
ABSTRACT
Opioid misuse is a public health crisis in the United States. In response, the FDA has approved drug products with abuse-deterrent features to reduce the risk of prescription opioid abuse. Abuse-deterrent formulations (ADFs) typically employ physical or chemical barriers or incorporate agonist-antagonist combinations as mechanisms to deter misuse. This study aims to assess the impact of abuse-deterrent properties, specifically ion-exchange resin complexation as a chemical barrier, on a model drug, promethazine hydrochloride (PMZ) tablets. Various formulations were developed through twin-screw wet granulation (TSWG) followed by twin-screw melt granulation (TSMG). In the TSWG process, the drug interacts with the resin through an exchange reaction, forming a drug-resin complex. Additionally, the study explored factors influencing the complex formation between the drug and resin, using the drug loading status as an indicator. DSC and ATR studies were carried out to confirm the formation of the drug-resin complex. Subsequently, hot melt granulation was employed to create a matrix tablet incorporating Kollidon® SR and Kollicoat® MAE 100P, thereby enabling sustained release properties. The drug-resin complex embedded in the matrix effectively deters abuse through methods like smoking, snorting, or parenteral injection, unless the drug can be extracted. In order to assess this, solvent extraction studies were conducted using an FDA-recommended solvents, determining the potential for abuse. Further investigations involved dissolution tests in change-over media, confirming the extended-release properties of the formulation. Results from dissolution studies comparing the ground and intact tablets provided positive evidence of the formulation's effectiveness in deterring abuse. Finally, alcohol-induced dose-dumping studies were conducted in compliance with FDA guidelines, concluding that the formulation successfully mitigates dose dumping in the presence of alcohol.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Formulaciones Disuasorias del Abuso / Trastornos Relacionados con Opioides Límite: Humans Idioma: En Revista: Eur J Pharm Biopharm Asunto de la revista: FARMACIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Formulaciones Disuasorias del Abuso / Trastornos Relacionados con Opioides Límite: Humans Idioma: En Revista: Eur J Pharm Biopharm Asunto de la revista: FARMACIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos