ABSTRACT
Poly(lactide-co-glycolide) (PLGA)-based formulation is one of the most often used parenteral extended-release forms to deliver various therapeutics. VIVITROL® as a commercialized PLGA microsphere formulation encapsulates naltrexone, a narcotic antagonist for opioid addiction and alcohol dependency. However, no U.S. Food and Drug Administration-approved generic product of naltrexone PLGA microsphere formulation has entered the market. The availability of generic naltrexone PLGA microspheres in low-income countries will broaden patients' accessibility to the safe, effective, and more affordable drug. A major challenge in developing such generic forms is the sensitivity of the drug-loaded microspheres' critical characteristics to the small manufacturing changes, even in formulations with the same compositions as the reference product. In this study, we evaluated the different key manufacturing parameters on the physicochemical, in vitro and in vivo release characteristics of naltrexone microspheres to develop a generic form of naltrexone PLGA microspheres. The selected formulations demonstrated a significant similarity in physicochemical characteristics and release profiles (f2 > 50) to the reference product, VIVITROL®. A strong relationship was observed between in vitro release profile of naltrexone as against its corresponding in vivo profile. It helped to roughly predict the in vivo release behavior of the different manufactured formulations by their corresponding in vitro release profiles.
