Synthesis and Characterization of Novel Sulphoxide Prodrug of Famotidine

Abstract:

Background of the work: Famotidine, a H₂ receptor antagonist is the drug of choice to treat ulcers in stomach (gastric and duodenal), erosive esophagitis (heartburn or acid indigestion) and gastroesophageal reflux disease (GERD). Drug molecules with limited aqueous solubility are becoming increasingly prevalent in the research and development portfolios of discovery focused pharmaceutical companies. Prodrugs are an established concept to overcome barriers like poor solubility to drug’s usefulness. Methods: As aqueous solubility is an important parameter to enhance the bioavailability of drug, novel sulphoxide prodrug of famotidine was synthesized. The synthesized prodrug was characterized by IR, NMR, Mass and DSC. Physicochemical characterization was done by partition coefficient and aqueous solubility studies. Chemical hydrolysis study was done in simulated gastric and intestinal fluids. Results and discussion: Decrease in Log P value, -0.74 of sulphoxide prodrug compared to -0.60 of famotidine, indicates the increase in hydrophilic property of synthesized sulphoxide derivatives of famotidine. Aqueous solubility increment of 6.7 fold was found in sulphoxide prodrug compared to famotidine. Invitro chemical hydrolysis profiles revealed that the synthesized sulphoxide derivatives of famotidine are chemically stable in Simulated Gastric fluid pH 1.2 and Simulated Intestinal Fluid pH 7.4. Conclusion: Hence the synthesized novel sulphoxide prodrug shown better aqueous solubility than existing drug and can be effectively used in therapy.

Key words: Famotidine, Sulphoxide prodrug, Characterization, aqueous solubility, Characterization, Chemical Hydrolysis, Log P.