Compatibility of intravenous ibuprofen with lipids and parenteral nutrition, for use as a continuous infusion

Abstract

There is increasing interest to administer ibuprofen as a continuous infusion instead of a traditional bolus for treating Patent Ductus Arteriosus (PDA). However, its compatibility data with commonly used drugs in the neonatal period, including parenteral nutrition (PN) and lipids is unavailable. The aim is to determine the compatibility of intravenous ibuprofen lysine with various ANZNN parenteral nutrition consensus group standard neonatal PN formulations and lipids. The PN and lipid solutions used in a tertiary neonatal unit were obtained. These included a Starter, Standard Preterm and low carbohydrate PN, and IV SMOF lipid admixture (SMOFLipid 20% 15 mL; Vitalipid N infant 4 mL, Soluvit N 1 mL) plus vitamin mixtures. 10% glucose was used as a control. 1:1 mixtures of different concentrations (1.25 to 5mg/mL) of ibuprofen lysine and each of the PN/glucose/lipid formulations were made. Samples were taken at hourly intervals for a total of 4 hours and tested for both physical (visual assessment, pH and microscopy) and chemical compatibility (High Performance Liquid Chromatography analysis). Zeta potential and particle diameter were measured for SMOF lipid admixture and ibuprofen combination to assess emulsion stability. 24 hour stability of ibuprofen dilution in 5 mL BD Luer-lok polypropylene syringes at 25°C was also assessed. Most PN formed opaque solutions when mixed with ibuprofen 2.5 and 5mg/mL solutions. However, ibuprofen dilution of 1.25mg/mL produced clear, colourless solutions with no microscopic particles when mixed with all PN/glucose/lipid formulations tested. Ibuprofen was chemically stable with all PN and SMOF lipid admixture, for a period of 4 hours. The zeta potential and particle diameter were within acceptable limits. Ibuprofen lysine was stable over 24 hours in Luer-lok polypropylene syringes. Ibuprofen 1.25mg/mL is physically and chemically compatible with 10% glucose, starter PN, standard preterm and low carbohydrate PN, and SMOF lipid admixture plus vitamins for a period of four hours, which is the maximum time they could be in an admixture during a continuous infusion.

Toward Safe Pharmacotherapy: The Interplay between Meropenem and Parenteral Nutrition Admixtures

“…The most frequent interactions involved drug or PN admixture ingredient precipitation, the formation of large lipid droplets exceeding the critical acceptance limit for intravenous administration, loss of homogeneity of the oil-in-water system, or color change. Such incompatibilities were reported in previous studies [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] ( Table 1 ). Interpretation of the results of drug–PN compatibility tests and their adaptation into clinical practice should be based not only on the conclusion whether the drug is or is not compatible with PN admixture, but also involve a detailed analysis of the pharmaceutical preparation of the drug (pH, excipients, solubilizers), the composition of the PN admixture (electrolyte content, type of lipid emulsion), and its physicochemical properties (pH, osmolarity) [ 2 , 16 , 17 , 18 ].…”

Effect of Lipid Emulsion on Stability of Ampicillin in Total Parenteral Nutrition

“…However, we chose pH, the particle size of the lipid emulsions by DLS and LD techniques, and the zeta potential. Such methods were used for investigating the stability of TPN admixtures by Garcia et al [3], Mediavilla et al [4], and Riera et al [5]. These parameters can be used for a quick and easy assessment of the stability of lipid emulsions, such as TPN admixtures.…”

“…There are few reports in the literature regarding physicochemical compatibility and stability of TPN admixtures and IV drugs. However, in recent years this topic has attracted more attention [1,2,3,4,5]. Administration of a drug with unknown stability is a direct threat to a patient’s health and life.…”

Development, Validation, and Stability Assessment Application of RP-HPLC-DAD Method for Quantification of Ampicillin in Total Parenteral Nutrition Admixtures

“…The co-administration of drugs and TPN admixtures is an important clinical problem. In recent years, this subject is being increasingly undertaken, and the results that were obtained in those studies can be applied in clinical practice [3][4][5][6][7]. Most of the researchers undertake the problem of the compatibility of drugs with TPN admixtures to determine the possibility of their simultaneous administration via Y-site to the same vascular access.…”