SOLUBILITY, STABILITY AND IONIZATION BEHAVIOR OF FAMOTIDINE

The pK(a) of famotidine was determined at 23 +/- 0.2-degrees-C to be 6 .76, 6.98 and 6.89 by a spectrophotometric, solubility, and partitioni ng method, respectively. The pH-solubility profile of famotidine indic ated an intrinsic solubility of 2.7 mm at 23-degrees-C. Degradation of famotidine followed pseudo-first-order kinetics over a pH range of 1- 11 at 37 +/- 0.2-degrees-C and at an ionic strength (mu) of 0.5. The p H-rate profile was accounted for by the specific acid and base catalys ed reactions as well as water-catalysed decomposition of both protonat ed and free famotidine. A pK(a) of 6.60, determined by potentiometry a l 37 +/- 0.5-degrees-C (mu = 0.5), was used in the kinetic calculation s. Maximum stability occurred at pH 6.3. Undissociated acetic acid, di hydrogen phosphate ion and glycine anion were found to contribute to t he general acid and base catalyses. pH-dependency of the apparent octa nol-water partition coefficient of famotidine indicated a partition co efficient of 0.23 for free famotidine at 23 +/- 0.2-degrees-C.