Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Pharm Dev Technol. 2023 Feb;28(2):190-199. doi: 10.1080/10837450.2023.2172041. Epub 2023 Jan 29.
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, and 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 (2 > 50) to the reference product, VIVITROL. A strong relationship was observed between release profile of naltrexone as against its corresponding profile. It helped to roughly predict the release behavior of the different manufactured formulations by their corresponding release profiles.
聚(乳酸-共-乙醇酸)(PLGA)制剂是最常用于将各种治疗药物递送至体内的注射型延长释放制剂之一。VIVITROL 是一种商业化的 PLGA 微球制剂,其中包封了纳曲酮,纳曲酮是一种阿片类药物成瘾和酒精依赖的麻醉拮抗剂。然而,没有美国食品和药物管理局批准的纳曲酮 PLGA 微球制剂的通用产品进入市场。在低收入国家提供通用的纳曲酮 PLGA 微球将扩大患者获得安全、有效和更负担得起的药物的机会。开发此类通用制剂的主要挑战是载药微球的关键特性对微小制造变化的敏感性,即使在与参比产品具有相同成分的制剂中也是如此。在这项研究中,我们评估了不同的关键制造参数对纳曲酮微球的理化性质和释放特性的影响,以开发一种通用的纳曲酮 PLGA 微球制剂。所选制剂在理化特性和释放曲线(2>50)方面与参比产品 VIVITROL 具有显著的相似性。纳曲酮的释放曲线与其相应的吸收曲线之间存在很强的相关性。它有助于通过相应的释放曲线大致预测不同制造制剂的释放行为。