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

Using an HPLC method, the effect of pH, two buffer species (phosphate and citrate), ionic strength, and temperature on the stability of acetozolamide has been studied. The optimum pH of stability appears to be 4. The buffers and ionic strength did not affect the decomposition constant. There was a direct relationship between the activation energies and pH values, with an energy of activation (Ea) value of 16.61 kcal/mol at pH 4. The un-ionized acetazolamide is subject to specific acid-base catalysis. The KH and KOH values have been estimated to be 0.23 and 1.56 d-1, respectively. These preformulation studies can be used to develop a stable oral liquid dosage form of acetazolamide.