Leaching rate of Diethylhexyl Phthalate (DEHP) from PVC containers with IV administrated lipid nanoparticle formulations

Lipid nanoparticle (LNP) formulations have been used to encapsulate and deliver small interfering RNAs (siRNAs) to the in-vivo targets for gene silencing through an intravenous (IV) administration. Diethylhexyl phthalate (DEHP), a commonly used plasticizer, is often present in IV bag materials and could be potentially leached into parental drug products. In this study, we investigated the extent of DEHP leaching in IV bags with LNP saline solution over a use time of administration for 24 h. The data showed that the amount of DEHP in LNP saline solution increased with increasing time in contact with IV bag materials and exceeded the safety limit set by FDA (3 mg per day or 30 ppm according to proposed dose) after 8 h. DEHP amount in the bagged LNP saline solution was also found increased with increasing concentration of LNP in the IV bag, suggesting that DEHP leaching is primarily attributed to the presence of lipophilic LNP formulation. The effect of leached DEHP on encapsulation efficiency was also examined and no impact was observed. The results demonstrated that LNP drug product should be administrated using DEHP-free IV bags. [Display omitted] •Leachability of diethylhexyl phthalate (DEHP) from IV bags in the presence of lipid nanoparticle (LNP) formulation has been investigated.•DEHP amount in LNP saline solution exceeded the safety limit set by FDA (3 mg per day) after 8 h in contact with IV bag materials.•Although LNP integrity was not impacted by increasing DEHP level in LNP saline solution, standard IV bags (containing DEHP) is not recommended for administrating lipid containing formulations.