Aim A combination of sodium benzoate and sodium phenylbutyrate is used as intravenous therapy in hyperammonaemia at concentrations up to 50 mg/mL. Currently, concentrated solutions of each component are available. The preparation relies on the accurate measurement of each component in a syringe or bag which then mixes via a Y-site, immediately prior to administration. A ready mixed product would potentially confer improvements in safety and convenience. An improvement would be the availability of a pre-mixed product, which requires less manipulation prior to administration. The aim of this work was to evaluate the chemical stability of a mixed system of sodiumbenzoate and sodium phenylbutyrate in glucose 10%, with relevant packaging conditions both at room temperature and at accelerated- degradations temperatures, with exposure to ultra violet (UV) light. Successful demonstration of compatibility across a range of conditions may provide impetus for the manufacture of pre-mixed intravenous therapy. This would improve efficiency of intravenous drug preparation and administration with the associated patient safety benefits of more accurate drug concentrations.
Method The chemical stability of sodium benzoate and sodium phenylbutyrate was monitored by measuring concentrations using high-performance liquid chromatography. The stability of the mixed system was evaluated at a range of concentrations(20 mg/mL, 25 mg/mL, 30 mg/mL, 40 mg/mL and 50 mg/mL) of both components in solutions of 10% w/v glucose in deionised water stored at three temperatures; refrigerated (4°C–8°C), at room temperature (20°C–25°C), and at 37°C. Glass and plastic were compared as packaging materials both with and without exposure to UV light. All mixed solutions were stored for up to 12 weeks.
Results Drug content remained above 98% for all mixed systems at all conditions for 12 weeks.
Conclusion Combination mixed systems of sodium benzoate and sodium phenylbutyrate were found to be stable for up to 12 weeks when stored in glass or plastic containers, exposure to high temperatures and UV light did not significantly affect the concentration of the drug present. This stability data will allow institutions to prepare pre-mixed solutions in advance for sodium benzoate and sodium phenylbutyrate in 10% glucose.It has patient safety benefits as it provides support of current clinical practice of the IV drug compatibility of sodium benzoate and sodium phenylbutyrate. It also provides quantitative reassurance in larger patients where current practice is to add the two drugs to a single bag for infusion. Moreover, it may also pave the way for commercial manufactured solutions of sodium benzoate and sodium phenylbutyrate to be produced. In practice, l-arginine is given via a Y-site alongside the two components,and work is currently underway repeating the study with all three components to assess compatibility.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.