Add time:08/14/2019         Source:sciencedirect.com

In the present study, novel less-painful tocol emulsions for the intravenous delivery of clarithromycin were prepared and optimized. The therapeutically effective concentration of clarithromycin, 5 mg/ml, was achieved using tocopherol succinate (TS) combined with oleic acid as lipophilic counterions. The possibility of employing the microdialysis technique to investigate the distribution of the drug in emulsions was explored. A three-level three-factorial Box–Behnken experimental design was utilized to conduct the experiments. The effects of selected variables, tocopherol succinate/oleic acid relation, poloxamer 188 content and 0.1 M NaOH amount, on three considered responses were investigated. The particle size, ζ potential and the oil phase distribution of clarithromycin for the optimized formulation were observed to be 138.5 nm, −32.16 mV and 97.28%, respectively. The emulsions prepared with the optimized formula demonstrated good physical stability during storage at 4 °C and room temperature. The histopathological examination for rabbit ear vein irritation test indicated that the irritation of clarithromycin could be eliminated by formulating the drug in a tocol emulsion.

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