Solvent-free method for masking the bitter taste of azithromycin dihydrate using supercritical fluid technology

Abstract

Introduction and purpose

The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 − 7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO₂. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer.

Methods

A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO₂) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors.

Results

The use of the supercritical technique at 40 °C and 10 MPa for 2 h allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin’s bitter taste.

Conclusions

Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients.