Crystalline and amorphous famotidine malate as pathways to prevent polymorphic transformation with improved...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Famotidine (FMT) exhibits poor oral bioavailability due to low solubility and permeability.
• The market withdrawal of ranitidine increases interest in famotidine solid-state modifications.
• Crystal engineering and co-amorphous strategies can improve drug pharmacokinetic performance.

Purpose of the Study:

• To develop novel solid forms of famotidine with enhanced properties.
• To investigate the formation and characteristics of famotidine malate crystalline salt and amorphous co-former.
• To assess the solubility and physical stability of the new famotidine solid forms.

Main Methods:

• Solvent evaporation and mechanochemical synthesis were employed.
• Powder X-ray diffraction (PXRD) and Differential Scanning Calorimetry (DSC) were used for characterization.
• Solubility assays in water and simulated gastric fluid were performed.

Main Results:

• Two novel solids were successfully prepared: crystalline famotidine malate (FMT-MT) and an amorphous phase (FMT-MTa).
• FMT-MT is a salt formed via proton transfer, exhibiting a specific crystal structure (P21/n).
• Amorphous FMT-MTa demonstrated good physical stability at 4°C for 60 days.
• Both FMT-MT and FMT-MTa showed significantly increased aqueous solubility (2.02- and 2.68-fold, respectively) compared to the marketed famotidine polymorph.

Conclusions:

• Co-crystal and amorphous strategies are effective for improving famotidine's solubility.
• The developed famotidine malate salt and amorphous form offer potential for enhanced drug delivery.
• These findings provide valuable insights for famotidine formulation development.