Development of taste-masking microcapsules containing azithromycin by fluid bed coating for powder for suspension and in vivo evaluation.

This research aims to develop bitter taste-masking microcapsules containing azithromycin (AZI) by a simpler and familiar method, fluid-bed coating technology, in comparison with Zithromax®. Cores of microcapsules, AZI microparticles, were prepared by fluid-bed granulation, then taste-masking polymer was covered on by fluid-bed coating technique. Eudragit L100, Eudragit RL100, and ethyl cellulose in single and combined with Eudragit L100 and Eudragit E100 were used as taste-masking polymers. The obtained microcapsules were characterised by taste-masking ability, in vitro release, SEM, coating thickness, and coating efficiency. Combination of ethyl cellulose and Eudragit E100 (3:1) in coating thickness of 45.13 ± 2.12% w/w prevents AZI release from microcapsules below bitter taste threshold (1.78 ± 1.17 µg/ml). Bioavailability of powders containing AZI microcapsules and pH modulators (50 mg Na3PO4 and 35 mg Mg(OH)2) was not significantly different from the reference product (Zithromax®, Pfizer, New York, NY) in the rabbit model (p > 0.05). These results support the possibility of developing a generic product containing AZI.

Formulation and biopharmaceutical evaluation of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets.

The objective of this study was to prepare and evaluate some physiochemical and biopharmaceutical properties of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets. In the first stage of the study, the bitter taste masking microparticles were prepared by solvent evaporation and spray drying method. When compared to the bitter threshold (32.43µg/ml) of azithromycin (AZI), the microparticles using AZI:Eudragit L100=1:4 and having a size distribution of 45-212µm did significantly mask the bitter taste of AZI. Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H NMR) proved that the taste masking of microparticles resulted from the intermolecular interaction of the amine group in AZI and the carbonyl group in Eudragit L100. Differential scanning calorimeter (DSC) analysis was used to display the amorphous state of AZI in microparticles. Images obtaining from optical microscopy and scanning electron microscopy (SEM) indicated the existence of microparticles in regular cube shape with many layers. In the second stage, dispersible tablets containing microparticles (DTs-MP) were prepared by direct compression technique. Stability study was conducted to screen pH modulators for DTs-MP, and a combination of alkali agents (CaCO3:NaH2PO4, 2:1) was added into DTs-MP to create microenvironment pH of 5.0-6.0 for the tablets. The disintegration time of optimum DTs-MP was 53±5.29s and strongly depended on the kinds of lubricant and diluent. The pharmacokinetic study in the rabbit model using liquid chromatography tandem mass spectrometry showed that the mean relative bioavailability (AUC) and mean maximum concentration (Cmax) of DTs-MP were improved by 2.19 and 2.02 times, respectively, compared to the reference product (Zithromax®, Pfizer).