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

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 approximately 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 approximately 78.8 kJ/mol at pH 4.3. The un-ionized spironolactone is subject to general acid-base catalysis. The Kh and Koh values at 40 degrees C have been estimated to be 1.63 and 2.8 x 10(5) day-1, respectively. The HPO4(-2) ion had approximately 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.