PREPARATION AND CHARACTERIZATION OF SOLID DISPERSION FAMOTIDINE – MANNITOL BY CO-GRINDING METHOD

Abstract

ABSTRACTObjective: This study aims to prepare and characterize solid dispersion of famotidine using mannitol to enhance the solubility and dissolution rate.Methods: Solid dispersions were prepared by co-grinding method in 9 formulas. The ratio of famotidine and mannitol was varied (1:1, 1:2, 2:1 w/w),and each ratio was milled at three different times (30, 60, and 90 minutes). The physical mixture was also prepared as comparison at ratio 1:1 w/w.Solid dispersions were characterized by X-ray diffraction analysis, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry(DSC) analysis, scanning electron microscopy (SEM), particle size analysis, solubility, and dissolution rate study. The assay of famotidine was doneusing a UV spectrophotometer.Results: The highest solubility of famotidine in solid dispersion was obtained in F2 (ratio 1:2 and grinding time 30 minutes). The solubility of intactfamotidine, physical mixture, and solid dispersion F2 was 1.630±0.027, 2.757±0.096, and 3.272±0.076 mg/ml, respectively. X-ray diffractogram ofsolid dispersion F2 showed a decrease in the peak intensity of famotidine. Thermogram of DSC showed a decrease of famotidine melting point for bothphysical mixture and solid dispersion. Photomicrograph of SEM indicated the changes in morphology solid dispersion compared to intact substances.FTIR analysis showed no chemical interaction between famotidine and mannitol. The particle size analysis showed a reduction in the particle sizeof the solid dispersion. The dissolution result after 60 minutes was 85.029%, 86.166%, 92.057% for intact famotidine, physical mixture, and soliddispersion F2, respectively.Conclusion: Solid dispersion increased solubility and dissolution rate.Keywords: Solid dispersion, Famotidine, Mannitol, Co-grinding, Solubility.