Solubilization and dissolution of famotidine from solid glass dispersions of xylitol

Abstract

The aqueous solubility and dissolution of famotidine from solid glass dispersions of xylitol, prepared by the fusion method, were investigated. Both famotidine and xylitol exhibited minimal degradation during the fusion process. Famotidine alone and in the presence of xylitol was found to be relatively stable in water at 37 ± 0.5°C for at least 3 days: less than 4% degradation was observed at the end of 72 h. Solubility of famotidine from solid glass dispersions and physical mixtures containing varying proportions of famotidine and xylitol at 37 ± 0.5°C was found to be higher than that of famotidine alone in water. However, the solid glass dispersions were more effective in enhancing the solubility of famotidine. A 1:40 famotidine:xylitol dispersion produced greatest solubility enhancement (31%). The solubility of famotidine from physical mixtures increased linearly with the increase in xylitol concentration, but the relationship was not linear for glass dispersions. Dissolution studies on glass dispersions with famotidine:xylitol ratios of 1:1, 1:10 and 1:20 in water at 37 ± 0.5°C revealed a marked increase in the dissolution rate of famotidine from solid glass dispersions when compared to the dissolution rate of famotidine powder alone. The increase in the dissolution rate was greatest at the lowest drug level (1:20) with 100% of the drug dissolving within one minute. Thermograms of the solid glass dispersions obtained by differential scanning calorimetry showed no evidence of chemical interaction between famotidine and xylitol. The phase diagram of the dispersion system by the capillary tube method suggested the formation of a eutectic mixture of famotidine and xylitol at a drug:carrier ratio approaching 1:40.