Clavulanic acid partitioning in charged aqueous two-phase micellar systems

Clavulanic acid is a drug obtained by Streptomyces sp. Fermentation and therapeutically employed in association with β-lactamic antibiotics to avoid bacterial resistance. Its industrial purification involves several steps including liquid–liquid extraction with organic solvents. Therefore, new economical and ecological alternatives for this drug purification, such as aqueous two-phase micellar system (ATPMS), are of great interest. In this work we investigated clavulanic acid partitioning in ATPMS composed only by the nonionic surfactant, C10E4, as well as mixed systems with the addition of the cationic CTAB or anionic AOT surfactants. According to the results, a lowering in the partition coefficient (K) value was observed with increasing temperature to the C10E4 micellar system, with K going from 0.87 ± 0.03 (T = 21 °C) to 0.67 ± 0.18 (T = 28 °C), probably due to the more hydrophobic environment in the top micelle-rich phase as compared to the bottom micelle-poor phase. For the mixed micellar systems, electrostatic attraction or repulsion influenced drug partitioning. A K = 1.44 ± 0.02 was observed with CTAB/C10E4 (the drug was attracted to the micelle-rich phase) and K = 0.78 ± 0.30 was observed with AOT/C10E4 (the drug was slightly repelled to the micelle-poor phase). These results indicate the potential of mixed micellar systems for clavulanic acid purification.

► We studied clavulanic acid partitioning in aqueous two phase micellar systems.
► These systems provide a promising alternative for the drug purification.
► We show that electrostatic interactions influence drug partitioning.
► Best results were obtained with anionic/nonionic micellar system.