The Korean Journal of Food & Health Convergence (식품보건융합연구)

Korea Food & Health Convergence Association (한국식품보건융합학회)
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Effect of Polysorbate 80 and Benzyl Alcohol on the Solubility of Amiodarone Hydrochloride

  • LEONTIEV, Viktor (Department of Biotechnology, Belarusian State Technological University) ;
  • LAZOVSKAYA, Olesya (Department of Biotechnology, Belarusian State Technological University)
  • Received : 2019.05.16
  • Accepted : 2019.06.04
  • Published : 2019.09.30
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Abstract

Amiodarone hydrochloride is an antiarrhythmic agent which has low aqueous solubility and presents bioavailability problem. These properties are a challenge for the pharmaceutical industry. Inclusion of lipophilic compound in the hydrophobic core of micelles, i.e. self-assembled structures based on surfactants in aqueous solution, is one way of increasing the solubility. Intravenous formulation of amiodarone hydrochloride with polysorbate 80 as a detergent and benzyl alcohol as a co-solvent is used in medical practice. This paper aimed to study the effect of polysorbate 80 and benzyl alcohol on the water solubility of amiodarone hydrochloride. Formation of mixed micelles consisting of nonionic surfactant polysorbate 80 and cationic amiodarone with chloride counterion was investigated by fluorescence spectroscopy. Benzyl alcohol was found to decrease the stability of the mixed micelles and lead to crystallization of amiodarone hydrochloride. The greatest amounts of crystals formed at 4℃ for 30 days in the model drug solutions with polysorbate 80 concentrations of 100.1 mg/mL and 97.9 mg/mL. A change of the polysorbate 80 concentration and avoidance the use of benzyl alcohol are recommended to improve the stability of the parenteral dosage form. These results can open new perspectives in the optimization of amiodarone intravenous formulations.

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References

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