Solubility, Stability and Ionization Behaviour of Famotidine

Abstract

The pKa of famotidine was determined at 23 +/- 0.2 degrees C to be 6.76, 6.98 and 6.89 by a spectrophotometric, solubility, and partitioning method, respectively. The pH-solubility profile of famotidine indicated 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 pH-rate profile was accounted for by the specific acid and base catalysed reactions as well as water-catalysed decomposition of both protonated and free famotidine. A pKa of 6.60, determined by potentiometry at 37 +/- 0.5 degrees C (mu = 0.5), was used in the kinetic calculations. Maximum stability occurred at pH 6.3. Undissociated acetic acid, dihydrogen phosphate ion and glycine anion were found to contribute to the general acid and base catalyses. pH-dependency of the apparent octanol-water partition coefficient of famotidine indicated a partition coefficient of 0.23 for free famotidine at 23 +/- 0.2 degrees C.

Voltammetric determination of famotidine on a disposable pencil graphite electrode

“…Keeping in mind that in cyclic voltammetry the highest peak currents corresponding to the famotidine oxidation on PGE were obtained in ABS pH 4.06 and PBS pH 6.81 and due to the fact that famotidine maximum stability was reported to be at pH 6.30, 33 for further studies PBS pH 6.81 was selected as supporting electrolyte.…”

Enhancement of the Aqueous Solubility and Masking the Bitter Taste of Famotidine Using Drug/SBE-β-CyD/Povidone K30 Complexation Approach

“…It has been reported that poor lipophilicity, poor aqueous solubility and susceptibility to gastric degradation may contribute to the low and variable oral bioavailability of famotidine. 19 It is white to off-white crystalline powder, insoluble in cold water. Its solubility at 208C: 80% w/v in dimethyl formamide, 50% w/v in acetic acid, <0.01% w/v in ethanol, ethyl acetate and chloroform.…”

Stability Challenges in Drug Discovery

“…Counterions can be involved in catalysis for degradation of certain compounds [14] [15]. Different types of counterions can produce various rates of degradation.…”