Main author: Mostafa Ghasemisarabbadieh
Institution or Company: Science Institute, University of Iceland; Faculty of Pharmaceutical Sciences, School of Health Sciences, Unversity of Iceland; Calor ehf.
Co-Author, Institution or Company:
Sveinbjörn Gizurarson, Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland; Calor ehf.; Department of Pharmacy, College of Medicine, University of Blantyre. Benjamín Ragnar Sveinbjörnsson, Science Institute, University of Iceland; Calor ehf.
Introduction: Oxytocin is a cyclic nonapeptide used to induce labor and prevent bleeding after childbirth. Due to its instability, storage and transport of oxytocin formulations can be problematic in hot/tropical climates. The aim of this study was to investigate the effect of trehalose and select antioxidants (uric acid, butylated hydroxytoluene (BHT), and L-ascorbic acid) on oxytocin stability in solution. The effect of buffer composition and acetate buffer concentration was also studied.
Methods: Formulations with the additives were prepared, the samples stored at 50°C and the oxytocin amount remaining analyzed using HPLC at a several-day interval.
Results: The results showed acetate buffer works better than citrate/phosphate buffer for oxytocin stability, with lower acetate buffer concentrations (0.025 M or less) yielding improved oxytocin stability. Although known degradation pathways of oxytocin include oxidation, the antioxidants uric acid and BHT had negligible effect, while L-ascorbic acid led to significantly faster degradation. Despite trehalose’s reputation as a great stabilizer for biomolecules, it also had small to negligible effect on oxytocin stability.
Conclusion: The results gave us a clearer insight into the effects and importance of buffer choice and concentration. Furthermore, the antioxidants tested and trehalose were not found to improve oxytocin’s stability in aqueous solution. As trehalose is often considered a go to stabilizer for a wide range of biomolecules, it is important to be aware of the limitations when considering various additives.
