Reverse engineering the Ozurdex dexamethasone intravitreal implant

Mark A Costello; Joseph Liu; Yan Wang; Bin Qin; Xiaoming Xu; Qi Li; Nathaniel A Lynd; Feng Zhang

doi:10.1016/j.ijpharm.2023.122625

Reverse engineering the Ozurdex dexamethasone intravitreal implant

Int J Pharm. 2023 Mar 5:634:122625. doi: 10.1016/j.ijpharm.2023.122625. Epub 2023 Jan 20.

Authors

Mark A Costello¹, Joseph Liu¹, Yan Wang², Bin Qin², Xiaoming Xu³, Qi Li², Nathaniel A Lynd⁴, Feng Zhang⁵

Affiliations

¹ University of Texas at Austin, College of Pharmacy, Department of Molecular Pharmaceutics and Drug Delivery, Austin, TX, USA.
² 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.
³ U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Silver Spring, MD, USA.
⁴ University of Texas at Austin, McKetta Department of Chemical Engineering and Texas Materials Institute, Austin, TX, USA.
⁵ University of Texas at Austin, College of Pharmacy, Department of Molecular Pharmaceutics and Drug Delivery, Austin, TX, USA. Electronic address: Feng.Zhang@austin.utexas.edu.

PMID: 36690129
DOI: 10.1016/j.ijpharm.2023.122625

Abstract

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.

Keywords: Dexamethasone; Hot-melt extrusion; Implant; Ozurdex; PLGA; Reverse engineering.

MeSH terms

Dexamethasone*
Drug Implants
Glucocorticoids*
Intravitreal Injections
X-Ray Microtomography

Substances

Drug Implants
Dexamethasone
Glucocorticoids