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Background Contact between medical devices (MDs) and the drugs that they contain can lead to sorption phenomena (sometimes making the concentration administered to the patient uncertain), as well as migration phenomena. 1 Indeed, certain compounds used in the composition of MDs are likely, under certain conditions, to migrate into the preparation and be administered to the patient. Patient exposure to these compounds raises questions about the possible clinical consequences. During in-use assays performed on tacrolimus (TAC) eye drops formulated at 0.2 and 1 mg/ml,2 variations of TAC concentrations attributable to sorption phenomena were observed, as well as the leaching of an antioxidant additive, 2,4-di-tert-butylphenol (2,4 DTBP), mainly in the 0.2 mg/mL eye drops. These phenomena, observed only when the ophthalmic preparation passed through the dropper system containing a silicone valve, appear to be influenced by galenic parameters.Objectives The objective of this study is to evaluate the impact of different galenic formulation parameters on the migration of 2,4 DTBP and the sorption of TAC.Materials and Methods An experimental design was established by varying the concentrations of the active substance: TAC (0.04, 0.2, and 1 mg/mL), as well as those of the excipients: polyoxyethylene castor oil (KEL) (32, 80, and 200 mg/ml) and absolute ethanol (EtOH) (10 and 100 mg/ml), as well as the storage temperature (5°C and 25°C). The various formulations were placed in static contact for three days with silicone valves from a multi-dose ophthalmic device constituting the “contact” group and compared to a group without valves constituting the ‘control’ group. The concentration of 2,4 DTBP and TAC was monitored by liquid chromatography coupled with a UV-visible detector.Results There was no significant difference in TAC concentration between the control and contact groups. However, in all formulations in contact with the valves, 2,4 DTBP was detected and increased over time, whereas it was not detected in the control group samples. The migration capacity of 2,4 DTBP was mainly influenced by the TAC concentration: the higher the TAC concentration, the less 2,4 DTBP was extracted. To a lesser degree, the EtOH concentration promoted migration, while increasing KEL concentration and temperature limited it.Conclusion Our study highlighted the impact of formulation on the leaching of 2,4 DTBP from silicone valves. The decrease of its extraction in the presence of higher TAC concentrations may be related to the sorption of TAC or KEL on the surface of the valves. In the absence of toxicological data on the impact of 2,4 DTBP on the eye at the quantities found, cytotoxicity studies should be performed. In the meantime, manufacturers of delivery devices are encouraged to conduct leachability studies in real-world use situations.References and/or Acknowledgements 1. Lockhart H, Paine FA. Introduction to the packaging of pharmaceuticals and healthcare products. In: Lockhart H, Paine FA, éditeurs. Packaging of Pharmaceuticals and Healthcare Products. Boston, MA: Springer US; 1996. p. 1‑12.2. Barrieu M, Chennell P, Yessaad M, Bouattour Y, Wasiak M, Jouannet M, et al. Physicochemical stability of a novel tacrolimus ophthalmic formulation for the treatment of ophthalmic inflammatory diseases. Pharmaceutics. Janv. 2022;14(1):118.