University of Texas at Austin, College of Pharmacy, Department of Molecular Pharmaceutics and Drug Delivery, Austin, TX, USA.
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, Silver Spring, MD, USA.
Int J Pharm. 2023 Mar 5;634:122625. doi: 10.1016/j.ijpharm.2023.122625. Epub 2023 Jan 20.
Ozurdex is a biodegradable implant formulated for sustained-release delivery of the corticosteroid dexamethasone to the posterior segment of the eye. The small, rod-shaped implant is administered directly to the vitreous using a dedicated applicator, and releases drug for up to 6 months after administration. Sustained release is achieved by embedding dexamethasone in a matrix of 50:50 poly(lactic-co-glycolic acid) (PLGA). In this work, the Ozurdex implant was thoroughly characterized to enable the reverse engineering of a compositionally and structurally equivalent implant. Advanced imaging techniques such as scanning electron microscopy (SEM) and microcomputed tomography (microCT) revealed that the Ozurdex implant exhibits an irregular surface and an internal porosity of 6% due to a large number of discrete voids approximately 3 μm in diameter. Thermal and spectroscopic analyses showed limited interaction between the drug and the polymer, resulting in a two-phase system of dexamethasone crystals embedded within a PLGA matrix. Reverse-engineered implants with properties similar to Ozurdex were prepared using a two-step hot-melt extrusion process. The reverse-engineered implants exhibited a triphasic drug release profile similar to Ozurdex. This work seeks to provide insight into the manufacturing process and characterization of PLGA-based solid implants to support future generic product development.
奥瑞珠单抗是一种可生物降解的植入物，用于将皮质类固醇地塞米松持续递送至眼部后段。这种小型棒状植入物使用专用的给药装置直接给药至玻璃体，在给药后长达 6 个月内释放药物。通过将地塞米松嵌入 50:50 聚（乳酸-共-乙醇酸）（PLGA）基质中实现了药物的持续释放。在这项工作中，对奥瑞珠单抗植入物进行了全面表征，以实现组成和结构等效植入物的反向工程。扫描电子显微镜（SEM）和微计算机断层扫描（microCT）等先进成像技术表明，奥瑞珠单抗植入物由于存在大量离散的直径约为 3 μm 的空隙，呈现出不规则的表面和 6%的内部孔隙率。热分析和光谱分析表明，药物与聚合物之间的相互作用有限，导致地塞米松晶体嵌入 PLGA 基质中的两相体系。使用两步热熔挤出工艺制备了具有与奥瑞珠单抗类似性能的反向工程植入物。反向工程植入物表现出类似于奥瑞珠单抗的三相药物释放曲线。这项工作旨在深入了解基于 PLGA 的固体植入物的制造工艺和特性，以支持未来的通用产品开发。
