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

Abstract

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Amiodarone hydrochloride is an antiarrhythmic drug used to treat supraventricular tachycardia. However, there are currently no commercial pediatric forms available to treat young patients. Various oral formulations were previously reported in the literature, but the concentration was lower than the doses prescribed in clinical practice (a loading dose of 500mg/m2/day for 7-10 days followed by a maintenance dose of 250mg/m2/day). The objective of this study was to develop an oral liquid formulation of amiodarone hydrochloride at an optimal concentration for use in children and to evaluate its physicochemical and microbiological stability. No commercial suspension vehicle was used, allowing the choice of excipients. Compounding was performed using hydroxypropylmethylcellulose as thickener, potassium sorbate preservative, citric acid/sodium citrate buffer, sodium saccharin as a , and a strawberry flavoring agent. A concentration of 40mg/mL was selected based on a 5-year compilation of prescribed doses. Analyses performed were the following: visual and microscopic inspection, testing for antimicrobial preservation, osmolality and pH measurements, quantification of amiodarone hydrochloride by a stability-indicating liquid chromatography method, and a microbiological count. At least 95% of the initial amiodarone hydrochloride remained stable during the 60-day study period under refrigeration. All other tested parameters remained stable at 5 °C. A targeted log reduction of the microorganism inoculum by day 14 and no microbial growth by day 28 were demonstrated in the test for antimicrobial preservation. The stability of 40mg/mL amiodarone hydrochloride oral suspension was maintained under refrigeration for 60 days before opening bottles and for 1 month after opening bottles.