Impact of polymer source variations on hydrogel structure and product performance in dexamethasone-loaded ophthalmic inserts.

Localized drug delivery can enhance therapeutic efficacy while minimizing systemic side effects, making sustained-release ophthalmic inserts an attractive alternative to traditional eye drops. Such inserts offer improved patient compliance through prolonged therapeutic effects and a reduced need for frequent administration. This study focuses on dexamethasone-containing ophthalmic inserts. These inserts utilize a key excipient, polyethylene glycol (PEG), which forms a hydrogel upon contact with tear fluid. Developing generic equivalents of PEG-based inserts is challenging due to difficulties in characterizing inactive ingredients and the absence of standardized physicochemical characterization methods to demonstrate similarity. To address this gap, a suite of analytical approaches was applied to both PEG precursor materials sourced from different vendors and manufactured inserts. 1H NMR, FTIR, MALDI, and SEC revealed variations in end-group functionalization, impurity content, and molecular weight distribution of the excipient. These differences led to changes in the finished insert network properties such as porosity, pore size and structure, gel mechanical strength, and crystallinity, which were corroborated by X-ray microscopy, AI-based image analysis, thermal, mechanical, and density measurements. In vitro release testing revealed distinct drug release profiles across formulations, with swelling rate correlated to release rate (i.e., faster release with rapid swelling). The use of non-micronized and micronized dexamethasone also contributed to release profile differences. Through comprehensive characterization of these PEG-based dexamethasone inserts, correlations between polymer quality, hydrogel microstructure, and release kinetics were established. The study highlights how excipient differences can alter product performance, emphasizing the importance of thorough analysis in developing generic equivalents of complex drug products.