Nanoemulsion-based strategy for azithromycin administration in pediatrics

Azithromycin (AZM) is a macrolide widely prescribed in pediatrics and is characterized by low solubility and bitterness. In this study, a dual-surfactant oil-in-water (O/W) nanoemulsion was optimized to overcome these limitations. High-Power Ultrasonic technique was used for emulsion production, using pumpkin seed oil as the internal O phase. At the same time, soy lecithin, a biodegradable and biocompatible phospholipid, was combined with Soluplus®, a high-molecular-weight amphiphilic polymer, to form a synergistic surfactant system. The O/W composition was optimized by a D-optimal experimental design to assess the influence of oil, surfactant and water percentages on droplet size, polydispersity index (PDI) and ζ-potential. The optimized formulation exhibited submicron droplet size (≈800 nm), low PDI (<0.08) and ζ-potential around −20 mV. Hydrophilic bentonite nanoclay was added to the final nanoemulsion, obtaining a product that remained physically stable for at least three months at 25 °C. The antimicrobial activity of the prepared nanoemulsion was confirmed by the agar diffusion method on four Gram-positive bacteria. Moreover, the time-kill test carried out on S. aureus showed that the nanoemulsion is active at a concentration of 23 μg/mL vs 400 μg/mL of the commercial suspension. A preliminary experiment, aiming to evaluate AZM interaction with the specific receptor (TAS2R4) for bitter taste perception, showed the nanoemulsion's ability to reduce AZM binding to the receptor, probably due to the combination of AZM confinement in the droplet and bentonite presence in the formulation, suggesting its potential as a valuable alternative for AZM oral administration.