Solubility, stability and ionization behaviour of famotidine.
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.
Islam
M S
MS
Division of Pharmaceutics, School of Pharmacy Northeast Louisiana University, Monroe 71209.
Narurkar
M M
MM
D002021:Buffers; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004355:Drug Stability; D015738:Famotidine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007700:Kinetics; D000442:Octanols; D012995:Solubility; D013053:Spectrophotometry / Q000379:methods; D014867:Water
D002021:Buffers; D007477:Ions; D000442:Octanols; D014867:Water; D015738:Famotidine