Insights into the interactions between ibuprofen arginine salt and parenteral nutrition: Assessment methods and...

In the past decade, ibuprofen (IBF) infusion solutions with concentrations of 4 mg/mL and 6 mg/mL have been introduced into the pharmaceutical market. Due to the poor water solubility of IBF, these formulations incorporate arginine as an excipient, enabling the formation of a soluble salt known as IBF arginate. This study investigated the compatibility of IBF formulations with five commercially available parenteral nutrition (PN) multi-chamber bag mixtures.

IBF and PN were combined in proportions based on the administration rates recommended by the manufacturers for both the drug and the PN multi-chamber bag. The compatibility of IBF + PN was evaluated through visual inspection, pH and osmolality measurements, particle size analysis, polydispersity assessment, and zeta potential analysis. Additionally, the PFAT5 parameter was determined. To measure turbidity, lipid-free PN solutions were prepared by substituting the volume of the lipid emulsion with water for injections. All evaluations were conducted immediately after mixing the drug with the PN and again after 4 hours of storage.

The IBF + PN samples formed a white emulsion without visible signs of destabilization or sediment. The pH of the IBF + PN samples ranged from 6.0 to 6.9, and the osmolality ranged from 457 to 1054 mOsm/kg. After 4 hours, the pH changes did not exceed 0.1 pH units, and the osmolality changes were within 3%. The mean particle size of the lipid emulsion ranged from 222 to 375 nm. In six cases, a second particle fraction with a size exceeding 4 µm was observed after 4 hours of storage. The PFAT5 parameter of all samples remained within 0.002% to 0.025% throughout the experiment. The turbidity of all IBF samples mixed with lipid-free PN ranged from 0.9 to 939 NTU, with the exception of IBF samples combined with the lipid-free, electrolyte-free PN model, which exhibited turbidity levels of ≤0.302 NTU.

Administering IBF solutions through a single infusion line with PN poses a risk to patient safety as it, in many cases, causes sediment formation. These interactions between IBF and PN electrolytes may not be detectable by visual inspection alone, highlighting the importance of turbidimetric analysis of lipid-free PN + drug combinations as a critical component of drug-PN compatibility assessment.