Impact of Material and Manufacturing Process on Performance of an Ophthalmic Implant

Abstract

Purpose : Dextenza (dexamethasone ophthalmic insert, NDA 208742) is an ophthalmic insert containing 0.4 mg of dexamethasone. It is a 3 mm cylindrical-shaped, resorbable, intracanalicular insert indicated for the treatment of ocular inflammation and pain following ophthalmic surgery. In this work, we delve into in vitro characterization of the implant to address challenges in determining qualitative (Q1) and quantitative (Q2) sameness and uncertainties associated with identifying appropriate characterization parameters (Q3) associated with this drug product.

Methods : An in vitro release testing (IVRT) method was developed to analyze in vitro release of API. Effect of implant size as well as surface area (diffusion) on release of API were compared using parameters described in the official USP monograph. Cure kinetics of hydrogel during processing and morphology of implants were also assessed.

Results : To form a hydrogel network, insoluble dexamethasone drug substance as a mixture with other aqueous excipients undergo a solution-phase crosslinking reaction to form the hydrogel network. Control of the pH was found to be critical which also influenced reaction rates, a process parameter that may be critical for shape forming of the implant. API were found to remain in solid form during and after processing. IVRT profile of samples was also assessed. Rate of API release was found to be governed by solubility limit of API in release medium as well as diffusion of the drug through hydrogel following the Higuchi release model (Figure 1). Together, these two limiting factors slow down API release, leading to a sustained released.

Conclusions : Several in vitro characterization methods were developed to evaluate manufacturing process and performance of a dexamethasone intracanalicular insert that uses a resorbable polyethylene glycol (PEG)-based hydrogel formulation. Our findings provide a better understanding on critical quality attributes (CQAs) and critical process parameters (CPPs). Dexamethasone remained as solid particles dispersed in the hydrogel and the rate of drug release followed the Higuchi model.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1. Release profiles of implants at 3 different sizes. All implants had the same formulations but were made to different sizes. Rate of API release was found to be governed by solubility limit of API in release medium as well as diffusion of the drug through hydrogel following the Higuchi release model.