Stability of Binary Mixtures of Drugs at Different Concentrations and Temperatures

Abstract

Background and Objective: In order to avoid separate injections, admixtures of drugs are frequently used in palliative care setting. The objective of this work is to study the stability of binary mixtures of drugs (ondansetron and midazolam) at different concentrations and temperatures all prepared in 0.9% NaCl and stored into infusers and glass in all cases protected from light. Materials and Methods: Two methods have been employed to determine periodically the concentration of each drug in the mixtures (HPLC-UV and UV-vis spectrophotometry methods). The concentrations of the samples were: 0.1 mg mL-1 – 0.1 mg mL-1 and 0.5 mg mL-1 – 1.0 mg mL-1 of ondansetron and midazolam respectively; temperature of storage 25ºC and 37ºC. NaCl 0.9% was used as diluent in all cases. The containers to store each mixture were three infusers and glass. Results: All solutions were initially clear and colourless but visible particles appear, in all cases, into the infusers after two days since their preparation. Conclusions: The admixture of ondansetron and midazolam in NaCl 0.9% is recommended to use for a maximum of one day, at the concentrations evaluated, over time it tends to precipitate. Infuser conditioning decreases stability with respect to other conditions materials, so other stability studies may not be extrapolated if stored under different conditions.