Abstract
The needs for safe, therapeutically effective antidiarrheal combination continuously lead to effective treatment. When administered simultaneously, metronidazole–kaolin interactions have been reported by FDA but not studied. This paper is the first to study metronidazole–kaolin interactions. Adsorption isotherms of a metronidazole–kaolin antidiarrheal combination from aqueous solutions at an in vivo simulated pH conditions were obtained at 37±0.5°C. Langmuir constants for the adsorption are 10.8225, 41.3223mgg−1 and 11.60, 2.56lg−1 aimed at the monolayer capacity, and the equilibrium constant at pH 1.2 and 6.8, respectively. pH effect on adsorption of known concentration of metronidazole by kaolin was also studied over the range 1.2–8. A gradual increase in the adsorbed amount was noted with increasing the pH. Elution studies by different eluents showed that drug recovery from adsorbent surface was pH-dependent via competitive mechanism. The elution followed the sequence: 0.1M HCl>0.1M NaCl>H2O. Adsorption–desorption studies revealed physical adsorption. The equilibrium concentration of metronidazole decreased as the adsorbent concentration was increased in the systems.The dissolution profiles (USP) of commercially available tablets (Riazole® 500mg) were obtained alone and in the presence of either (ORS®) rehydration salts and 9 or 18g of kaolin powder. The percentage drug released versus time: 95.01% in 25min, 101.02% in 30min, 67.63% in 60min, 60.59% in 60min, respectively.The percentage drug released versus time was increased with ORS® due to common ion effect [Cl−], while, it was decreased with kaolin due to adsorption. The mechanism of reaction of Riazole® (500mg) tablets in the different dissolution media, confirms with Korsmeyer–Peppas model.The interaction between metronidazole and kaolin was characterized by melting point determinations, differential scanning calorimetry analysis and infrared spectroscopy. The results obtained were suggestive of physical interaction between metronidazole and kaolin.
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