Physicochemical and microbiological stability of 40 mg/mL amiodarone hydrochloride oral suspension

Area of Science:

• Pharmaceutical Sciences
• Pediatric Pharmacology
• Drug Formulation

Background:

• Amiodarone hydrochloride is a critical antiarrhythmic drug for supraventricular tachycardia.
• Lack of commercially available pediatric formulations necessitates specialized compounding.
• Existing oral formulations have concentrations below clinically prescribed pediatric doses.

Purpose of the Study:

• To develop a stable oral liquid formulation of amiodarone hydrochloride at a concentration suitable for pediatric patients.
• To evaluate the physicochemical and microbiological stability of the developed pediatric amiodarone hydrochloride formulation.

Main Methods:

• A 40 mg/mL amiodarone hydrochloride oral suspension was compounded using selected excipients (hydroxypropylmethylcellulose, potassium sorbate, citric acid/sodium citrate buffer, sodium saccharin, strawberry flavoring).
• Stability was assessed through visual/microscopic inspection, antimicrobial preservation testing, osmolality and pH measurements, and amiodarone hydrochloride quantification via stability-indicating liquid chromatography.
• Microbiological counts were performed throughout the study period.

Main Results:

• The amiodarone hydrochloride oral suspension maintained at least 95% of its initial concentration over 60 days under refrigeration (5 °C).
• Physicochemical parameters (pH, osmolality) remained stable.
• Antimicrobial preservation testing demonstrated a targeted log reduction of microorganisms by day 14 and no growth by day 28.

Conclusions:

• The developed 40 mg/mL amiodarone hydrochloride oral suspension is stable under refrigeration for 60 days prior to opening.
• The formulation remains stable for 1 month after opening the bottles.
• This formulation addresses the need for a stable, appropriately concentrated oral amiodarone hydrochloride option for pediatric patients.