Quality and stability of oral extemporaneous formulations developed from commercial tablets containing spironolactone

Abstract

The purpose of this study was to develop extemporaneous liquid pharmaceutical formulations from commercial tablets containing spironolactone and to assess their stability for use in children or adults with difficulty in swallowing. The content and stability of spironolactone in the tablets, as well as in water, 1.5% carboxymethylcellulose (CMC) or simple syrup dispersions were determined by high performance liquid chromatography (HPLC) analysis on a C18 silica column (250 mm x 4.6 mm x 5 µm), with a mobile phase of methanol:water (75:25 v/v), flowing at 1 mL/ min, and UV detection at 240 nm. The extemporaneous formulations were tested over a 35-day period at 8, 27, and 40 ºC. Drug content in the aqueous dispersion was far lower than expected, with significant fluctuations at all temperatures, owing to rapid sedimentation. The content proved adequate in aqueous 1.5% CMC dispersion at 27 ºC, with undesirable variations at the other temperatures. The syrup-based dispersion remained stable at all three temperatures, with suitable drug content and no significant variability. No degradation products were observed in any of the formulations. The syrup-based dispersion is easy to prepare, self-preserving, stable, palatable, offering satisfactory drug content per dose, and can therefore be recommended as an extemporaneous formulation for enhancing treatment adherence and effectiveness.