A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na+ and K+)

Avanti, Christina and Amorij, Jean-Pierre and Setyaningsih, Dewi and Hawe, Andrea and Jiskoot, Wim and Visser, Jan and Kedrov, Alexej and Driessen, Arnold J. M. and Hinrichs, Wouter L. J. and Frijlink, Henderik W. (2011) A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. Both monovalent metal ions (Na+ and K+). The AAPS Journal, 13 (2). pp. 284-290. ISSN 1550-7416

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Official URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC308569...

Abstract

In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. and divalent metal ions (Ca2+, Mg2+, and Zn2+) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl2, MgCl2, or ZnCl2 and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca2+, Mg2+, or Zn2+, while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions.

Item Type: Article
Uncontrolled Keywords: citrate buffer, divalent metal ions, improved stability, oxytocin
Subjects: Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
Depositing User: Eko Setiawan 194014
Date Deposited: 04 Feb 2013 06:13
Last Modified: 05 Feb 2013 02:41
URI: http://repository.ubaya.ac.id/id/eprint/3066

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