Synthesis and Characterization of Novel Sulphoxide prodrug of Famotidine

Abstract

Background of the work: Famotidine, a H 2 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.

Bromine‐Mediated C‐S Bond Formation: Synthesis of Thiazoles from α‐Methylene Ketones by Using Oxone Oxidative System

“…The Famotidine was an excellent histamine H 2 receptor blocker, which was used to treat and prevent ulcers in stomach and intestine [22] . Based on the above results, we investigated the various methylene ketones with amidinothiourea to synthesis of a series of Famotidine‐like thiazole fragments.…”

The Prodrug Approach: A Successful Tool for Improving Drug Solubility

“…This modification (compound 88 ) increased solubility in water 6.7-fold compared to famotidine (Figure 32). The prodrug was stable at pH 1.2 and 7.4 and might be effective in ulcer therapy [118].…”

Cocrystallization of Etodolac: Prediction of Cocrystallization, Synthesis, Solid State Characterization And In Vitro Drug Release

“…active pharmaceutical ingredients (aPI) with poor aqueous solubility are becoming more prevalent in the research and development portfolios of discovery focused pharmaceutical companies (1). Molecules of this type can encounter a number of challenges in pharmaceutical development and may subsequently lead to poor dissolution, poor systemic availability and consequent poor drug efficacy in patients, especially after oral administration.…”