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.
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.
Authors: Janneke P van Grafhorst; Norbert A Foudraine; Fleur Nooteboom; Wil H J Crombach; Nico J J Oldenhof; Hans van Doorne Journal: Crit Care Med Date: 2002-04 Impact factor: 7.598
Authors: Carola Dehmel; Stephan A Braune; Georg Kreymann; Michael Baehr; Claudia Langebrake; Heike Hilgarth; Axel Nierhaus; Dorothee C Dartsch; Stefan Kluge Journal: Intensive Care Med Date: 2011-04-30 Impact factor: 17.440
Authors: P R Kowey; J H Levine; J M Herre; A Pacifico; B D Lindsay; V J Plumb; D L Janosik; H A Kopelman; M M Scheinman Journal: Circulation Date: 1995-12-01 Impact factor: 29.690