Dextran sulfate/Triton X two-phase micellar systems as an alternative first purification step for clavulanic acid

Author(s)

Cardoso Silva, Marcela de Siqueira ^[1] ; Santos-Ebinuma, Valeria de Carvalho ^[2] ; Lopes, Andre Moreni ^[1] ; Rangel-Yagui, Carlota de Oliveira ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Biochem & Pharmaceut Technol, BR-05508 Sao Paulo - Brazil

^[2] UNESP State Univ Sao Paulo, Sch Pharmaceut Sci, Dept Bioproc & Biotechnol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Fluid Phase Equilibria; v. 399, p. 80-86, AUG 15 2015.
• Web of Science Citations: 5

Abstract

The development of efficient and cost-effective downstream processes is essential for any pharmaceutical products. Clavulanic acid (CA) is a beta-lactamic drug used combined with antibiotics to inhibit bacterial resistance mediated by beta-lactamase enzymes. CA industrial purification involves techniques such as liquid-liquid extraction with organic solvents and chromatographic techniques, resulting in low recovery yields. In this way, techniques more suitable for biomolecules such as liquid-liquid extraction based on aqueous two-phase systems, which contains 60-90% of water, are of great interest. In this work, aqueous two-phase micellar systems (ATPMS) formed by the nonionic surfactants Triton X-114 and Triton X-100 in the presence or absence of dextran sulfate (Dx-S) were investigated as a first step of CA purification. The drug was found to be stable in the presence of polymers and surfactants with mass balances higher than 80% for all the conditions evaluated. CA partitioning in ATPMS was investigated in the presence of concentrations of Dx-S lower than 4%, CA partitioned more to micelle-poor phase. However, increasing the polymer concentration (8 and 14%), we observed a phase inversion with both surfactants and the drug partitioned more pronounced to the micelle rich-phase, with partition coefficients up to 1.83 with TX-100. The results show that Dx-S/Triton X systems can be used as a first step of CA extraction and the conditions can be adjusted depending on the subsequent extraction methods. (c) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 11/18088-6 - Clavulanic acid partitioning in Triton X-100 aqueous two-phase micellar systems in the presence of salt or polymer
• Grantee: Nathália Barros Militão dos Santos
• Support type: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 10/02324-0 - Study of clavulanic acid partitioning using two-phase aqueous micellar system with salt or polymer addition
• Grantee: Marcela de Siqueira Cardoso Silva
• Support type: Scholarships in Brazil - Master