Solubility, stability and ionization behaviour of famotidine

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Drug Stability

Background:

• Famotidine is a histamine H2 receptor antagonist used to treat stomach acid conditions.
• Understanding its physicochemical properties is crucial for formulation and stability.
• Previous studies have explored various aspects of famotidine's behavior in solution.

Purpose of the Study:

• To determine the pKa and intrinsic solubility of famotidine.
• To investigate the degradation kinetics and pH-rate profile of famotidine.
• To characterize the partitioning behavior of famotidine across different pH values.

Main Methods:

• Spectrophotometry, solubility, and partitioning methods were used to determine pKa.
• Degradation kinetics were studied over a wide pH range at controlled temperature and ionic strength.
• Potentiometry was employed to determine pKa at physiological temperature for kinetic analysis.

Main Results:

• Famotidine exhibited pKa values around 6.7-7.0 across different methods and temperatures.
• Intrinsic solubility was found to be 2.7 mM at 23°C.
• Degradation followed pseudo-first-order kinetics, with maximum stability observed at pH 6.3.
• The partition coefficient for free famotidine was determined to be 0.23.

Conclusions:

• Famotidine's physicochemical properties, including pKa, solubility, and partition coefficient, were comprehensively characterized.
• The degradation pathway is influenced by specific acid, base, and water catalysis.
• Optimal pH for famotidine stability is approximately 6.3, guiding formulation development.