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Ready-to-use parenteral amiodarone: a feasibility study towards a long-term stable product formulation
  1. Maartje S Jacobs1,
  2. Marianne Luinstra1,2,
  3. Jan Reindert Moes1,
  4. Tiffany C Y Chan2,
  5. Isidor Minovic2,
  6. Henderik W Frijlink2,
  7. Herman J Woerdenbag2
  1. 1Department of Clinical Pharmacy, Martini Hospital, Groningen, The Netherlands
  2. 2Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Herman Woerdenbag, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands; h.j.woerdenbag{at}rug.nl

Abstract

Objectives To determine the feasibility of preparing a long-term stable ready-to-use parenteral amiodarone formulation using cyclodextrins as dissolution enhancer.

Methods A preformulation study was performed with different molar ratios of hydroxypropyl-beta-cyclodextrin (HP-BCD) or sulfobutylether-beta-cyclodextrin (SBE-BCD) to amiodarone in order to investigate enhancement of amiodarone's water solubility. Further, effects of pH and temperature on the dissolution rate during production were investigated. Shelf-life was determined for a ready-to-use iso-osmotic preparation of 1.8 mg/mL amiodarone with SBE-BCD in a molar ratio of 1:3. Amiodarone content was assessed using a validated high-pressure liquid chromatography ultraviolet method.

Results Amiodarone–SBE-BCD in a molar ratio of 1:3 at pH 4.0–5.0 yielded the best results in terms of increased solubility and dissolution time (90 min). With SBE-BCD, a smaller molar ratio to amiodarone was needed than with HP-BCD. The amiodarone content of the final formulation stored 12 months at 21°C in daylight remained unchanged.

Conclusions A ready-to-use or ready-to-administer amiodarone product, prepared in a hospital pharmacy, for intravenous application in an acute clinical setting is a feasible option from a chemical, physical and microbiological point of view. The availability of such a product will have a significant impact on medication safety, and production should therefore be considered.

  • intravenous amiodarone
  • pharmaceutical formulation
  • ready-to-use
  • cyclodextrins
  • sulfobutylether-beta-cyclodextrin

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