Stability of Extemporaneously Prepared Acetazolamide Oral Suspensions at Two Temperatures.

Abstract

Some drugs need to be compounded by the pharmacist before being administered to the patient. A study was conducted to determine the stability of acetazolamide suspensions in 2 different vehicles (Oral Mix and Oral Mix Sugar Free [SF]) from bulk drug and tablets at 2 different temperatures and in 2 different containers (amber plastic bottles and clear plastic syringes). Acetazolamide suspensions (25 mg/mL) were prepared from bulk drug or tablets. Each suspension, using Oral Mix or Oral Mix SF, was split between 2 types of containers-amber plastic bottles and clear plastic syringes-and stored either at room temperature (23°C-27°C) or under refrigeration (3°C-7°C). Samples were drawn from the suspensions right after preparation and on days 7, 14, 30, 45, 60, 75, and 90. They were then analyzed by high-performance liquid chromatography (HPLC) using a reverse-phase column. A validated stability-indicating HPLC with ultraviolet detection method was developed. A visual inspection and a pH measurement were also completed at each time point. Stability was defined as retention of at least 90% of the initial concentration of acetazolamide suspension. At least 91.2% of the initial acetazolamide concentration in suspensions remained throughout the 90-day study period for both vehicles, both containers, and both temperatures. Assays varied between 91.2% and 105.0% of the initial concentration for all 112 tested conditions but 2 (105.2% and 109.0%). Linear regression was calculated for each time profile and remained above 95.0% at the end of the study in all cases. Similarly, pH remained within 0.1 unit of the initial pH, which was 4.2 for Oral Mix and 4.3 for Oral Mix SF. Furthermore, no changes in organoleptic properties were observed because the preparations remained as white fluid suspensions without sedimentation. Acetazolamide suspensions were stable for at least 90 days in all tested conditions because the average drug concentration was not less than 90% of the initial concentration. The beyond-use date could be extended from 60 to 90 days.