Preformulation studies of spironolactone: Effect of pH, two buffer species, ionic strength, and temperature on stability

Article abstract of DOI:10.1002/jps.2600800611

Using a stability-indicating HPLC assay method, the effect of pH, two buffer species (citrate and phosphate), ionic strength, and temperature on the stability of spironolactone in 20% solution of ethyl alcohol in water has been studied. The optimum pH of stability appears to be ~4.5. On increasing the buffer concentration, both species hastened the decomposition of spironolactone. The ionic strength did not affect the stability of the drug. The energy of activation has been estimated to be ~78.8 kJ/mol at pH 4.3. The un-ionized spironolactone is subject to general acid-base catalysis. The K(h) and K(oh) values at 40 °C have been estimated to be 1.63 and 2.8 x 10⁵ day^-1, respectively. The HPO₄^-2 ion had ~10 times more catalytic effect than the H₂PO₄^-1 ion. This data will be used to develop a stable oral liquid dosage form of the drug.