Stability of Spironolactone in an Extemporaneous Preparation: Effect of Storage Temperature and Packaging Materials

Abstract

The objectives of this study were to study physical, chemical and microbiological stability of the extemporaneous spironolactone suspensions. An extemporaneous spironolactone suspension was prepared from commercially available spironolactone 25-mg tablets using compounded suspending vehicles. The final concentration of spironolactone formulation was 2 mg/mL. Samples were separately filled in HDPE, PET and amber glass bottles then stored in refrigerator at 5±3°C and room temperature (30±3° C). A sample was collected from each bottle immediately after preparation and after 7, 14, 30, 60, and 90 days. High performance liquid chromatography was used for quantitative analysis of spironolactone in each sample. The chemical stability of spironolactone in suspensions was determined by calculating the percentage of the remaining spironolactone on each sampling interval. The acceptable stability was defined as retention of at least 90% of the initial spironolactone concentration. The physical and microbiological stabilities were intermittently evaluated. At least 90% of the initialspironolactone concentration remained in the compounding suspensions for up to 30 days regardless of packaging material. There were no substantial changes in the appearance (color and consistency) of the samples stored at 5±3°C and room temperature (30±3°C). The pH values of the samples kept at room temperature decreased significantly compared to the initial pH value. The suspension maintained microbiologic stability for 30 days. In conclusion, utilizing the studied suspending vehicle for the compounding of 2.0 mg/mL spironolactone extemporaneous suspension afforded a stable preparation for a month long storage at room temperature regardless the filling bottle material.