Investigation of interactions between LDPE containers and ingredients of oil-based ophtalmic formulations

BACKGROUND: This study presents the results of an investigation into the interactions between innovative ophthalmic formulations and commercially available low-density polyethylene (LDPE) containers. The newly developed formulations are self-emulsifying oils (SEOs) containing suspended drug particles, designed to form an emulsion immediately upon contact with tear fluid. Physicochemical and mechanical properties of the containers were evaluated. Interactions between 6 different LDPE containers and the SEO matrix (oil "O" and surfactant Tween 20 "T") were investigated, and the impact of the SEO formulations on the mechanical properties of the containers was assessed. OBJECTIVES: The study aimed to identify potential interactions between SEO components and the packaging that may occur during storage under stress conditions, based on changes in morphology, structure, thermal behavior, and mechanical strength. MATERIAL AND METHODS: The SEO carrier was prepared by mixing Miglyol® 812 with Tween® 20 at a concentration of 5% w/w, followed by sterile filtration. The suspensions were compounded aseptically using sterile, micronized sodium cefuroxime (CEF) and vancomycin hydrochloride (VAN) at a concentration of 5% w/w, along with sodium citrate (2% w/w). In accordance with stability testing guidelines, stress stability studies were conducted in a climatic chamber at 40°C/75% relative humidity and 60°C/75% relative humidity. To detect structural and physicochemical changes, advanced analytical techniques were employed, including Fourier-transform infrared (FTIR) and near-infrared (NIR) spectroscopy for the assessment of structural alterations and potential degradation, differential scanning calorimetry (DSC) for thermal analysis, and X-ray diffraction (XRD) for evaluation of material crystallinity. The mechanical strength of packaging material fragments after contact with the formulations was evaluated using a TA.XTplus texture analyzer. RESULTS: The experiments indicated potential migration (e.g., of plasticizers and residual monomers), as well as adsorption or absorption of excipient components. Subtle interactions were observed, accompanied by negligible changes in the mechanical strength of the packaging material. CONCLUSIONS: The study confirmed the necessity of comprehensive compatibility testing between ophthalmic formulations and their packaging materials. A thorough understanding of these interactions is essential to ensure product stability, safety, and quality during storage and use.