Main author: Benjamín Ragnar Sveinbjörnsson
Institution or Company: Department of Chemistry, Science Institute, University of Iceland; Calor ehf.
Co-Authors, Institution or Company:
Mostafa Ghasemisarabbadieh, Department of Chemistry, Science Institute, University of Iceland; Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland; Calor ehf.. Sveinbjörn Gizurarson, Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland; Calor ehf.; Department of Pharmacy, College of Medicine, University of Malawi.
Introduction: Oxytocin is a nonapeptidic hormone that is one of the drugs of choice for the treatment of postpartum hemorrhage. Unfortunately, it is unstable at elevated temperatures which may be a contributing factor to poor oxytocin quality in some low and middle-income countries. It would therefore be beneficial to develop a stabilizing formulation. Previous studies have found that the free amino group on oxytocin contributes to rapid degradation kinetics. We, therefore, explored if crown ethers could be used to bind the amino group and slow down the degradation.
Methods: Oxytocin formulations with crown ethers were developed and the amount of oxytocin remaining was measured at a regular interval using HPLC. Additional formulations were measured using UV-Vis and NMR in an attempt to observe evidence of binding interactions.
Results: 18-crown-6 slowed down oxytocin’s degradation in citrate/phosphate buffer but sped up the degradation in acetate buffer. Evidence suggestive of binding interaction between the crown ether and oxytocin, were also observed in HPLC, UV-Vis, and NMR.
Conclusions: Understanding the mechanism of degradation and potential mechanisms of stabilization can help in improving stabilizing formulations. These results will hopefully aid in developing more efficient mechanistically guided stabilization approaches for oxytocin as well as for other thermolabile molecules.
