We aimed to develop a novel method for assessing the bitterness of azithromycin-containing reverse micelles(AM-containing RMs). Azithromycin-containing reverse mi-celles were prepared by processing Lipoid E80 and medi...We aimed to develop a novel method for assessing the bitterness of azithromycin-containing reverse micelles(AM-containing RMs). Azithromycin-containing reverse mi-celles were prepared by processing Lipoid E80 and medium chain triglycerides via a freeze-drying method. The bitterness threshold of azithromycin was determined by human tastetest, and an equation was derived to correlate the azithromycin concentrations and bitter-ness scores of standard solutions. Simulated salivary fluids and sampling times were fixedbased on the drug release profile of AM-containing RMs, with Zithromax ?(a commercialformulation of azithromycin) used as the control. The drug release concentrations fromstimulated salivary fluids were then used to assess the bitterness of AM-containing RMsand Zithromax ?. Afterward, the oral bioavailability of both formulations was evaluated byin vivo experiments in male Wistar rats. The results showed that the bitterness thresh-old of azithromycin standard solutions was between 25.3 μg/ml and 30.4 μg/ml. There-after, we calculated that the bitterness scores and the drug release concentrations of theazithromycin-containing reverse micelle formulation were similar to those of Zithromax ?ateach time point after 10 min of dispersal in simulated salivary fluid. In addition, the AUC 0-tafter oral administration of AM-containing RMs was 1.75-fold( P < 0.05) higher than that ofZithromax ?. In conclusions, a system for assessing bitterness was developed using an in vitrodrug release evaluation method and a human taste test panel. We found that the bitterness of azithromycin was successfully masked by reverse micelles, which also improved the oral bioavailability of azithromycin compared to that of Zithromax ?.展开更多
基金supported by The National Key Technologies R&D Program for New Drugs of China (2015ZX09J15104-003)
文摘We aimed to develop a novel method for assessing the bitterness of azithromycin-containing reverse micelles(AM-containing RMs). Azithromycin-containing reverse mi-celles were prepared by processing Lipoid E80 and medium chain triglycerides via a freeze-drying method. The bitterness threshold of azithromycin was determined by human tastetest, and an equation was derived to correlate the azithromycin concentrations and bitter-ness scores of standard solutions. Simulated salivary fluids and sampling times were fixedbased on the drug release profile of AM-containing RMs, with Zithromax ?(a commercialformulation of azithromycin) used as the control. The drug release concentrations fromstimulated salivary fluids were then used to assess the bitterness of AM-containing RMsand Zithromax ?. Afterward, the oral bioavailability of both formulations was evaluated byin vivo experiments in male Wistar rats. The results showed that the bitterness thresh-old of azithromycin standard solutions was between 25.3 μg/ml and 30.4 μg/ml. There-after, we calculated that the bitterness scores and the drug release concentrations of theazithromycin-containing reverse micelle formulation were similar to those of Zithromax ?ateach time point after 10 min of dispersal in simulated salivary fluid. In addition, the AUC 0-tafter oral administration of AM-containing RMs was 1.75-fold( P < 0.05) higher than that ofZithromax ?. In conclusions, a system for assessing bitterness was developed using an in vitrodrug release evaluation method and a human taste test panel. We found that the bitterness of azithromycin was successfully masked by reverse micelles, which also improved the oral bioavailability of azithromycin compared to that of Zithromax ?.
