## 7 Downstream Processing of CA
The rapid CA degradation in aqueous media has implications on the selection of the separation technology, the shorter the time of CA in aqueous solution, the lower its degradation. Furthermore, the complete CA desorption from the ion exchange matrix doubles the adsorption time, increasing the product losses. The layered double hydroxides (LDHs) have been also explored for CA adsorption from aqueous solutions. LDHs are mixed hydroxides with layers of divalent, trivalent cations, and hydroxyl anions capable of anion exchange [184]. The interlayer domain is constituted by water molecules and anions [184]. When using calcined hydrdcalcite LDHs containing 70% MgO in a solid-liquid ratio of 15.0 g:L\({}^{-1}\), complete adsorption of CA was observed [184]. CA adsorption into Zn\({}_{2}\)Cr-NO\({}_{3}\), Zn\({}_{2}\)Al-NO\({}_{3}\), and Mg\({}_{2}\)Al-NO\({}_{3}\) LDHs was satisfactory, but the best results were observed for the Zn\({}_{2}\)Cr-NO\({}_{3}\) LDH microencapsulated with calcium alginate, showing a purification factor of about 2.3 and CA recovery between 93 and 99% [185; 186]. Aqueous two-phase systems (ATPS) have been also studied for CA separation from fermentation broth. ATPS are formed when two hydrophilic components are mixed in water above a threshold concentration [187]. Two polymers or a polymer and a salt are commonly used. Those systems are convenient for the purification of bioactive compounds due to the high water content (70-90%) in both phases [187]. The use of ATPS for CA recovery from cultivation broth was first reported by [PERSON] and [PERSON] [188]. The authors used the ATPS of polyethylene glycol (PEG) and potassium phosphate for CA extraction. Under the conditions tested, CA showed high affinity to the PEG-rich (top) phase, yielding recoveries ranging from 90 to 99% [188]. The subsequent optimization studies confirmed the high recovery ratio of this technique, using PEG with molecular mass of 400 daltons at pH 6.4 and top/bottom phase volume ratios of 42 and 1.3, respectively [189]. Similar results have been observed when using other PEG based ATPS like those formed by PEG/citrate, PEG/polyacrylamide and PEG/cholinium chloride [187; 190; 191]. Furthermore, [PERSON] et al. [192] used ATPS followed by ion-exchange adsorption for CA separation from complex fermentation broth with high amino acids content. The ATPS-Ion exchange system produced CA recoveries of 100% in both stages, which is higher than the separation reached when using single ion-exchange adsorption. However, the CA degradation rate in ATPS systems remains to be assessed given the susceptibility of CA to hydrolysis via nucleophilic attacks to the carbonyl group [176]. [PERSON] and co-workers [193] investigated the application of ATPS in the CA extractive fermentation with a variant of _S. variabilis_ in the shake flask and bioreactor scales, taking advantage of the high extraction levels attained with this separation strategy. ATPS 25% PEG 8000 g:mol\({}^{-1}\) and phosphate salts led to CA productivity of 5.3 mg.(L h)\({}^{-1}\)[193]. The CA concentration in the PEG-rich phase was 691 mg. L\({}^{-1}\), which was 30% higher than in the cultivation broth [193]. In the bioreactor scale (950 rpm, 3.5 vvm), this strategy allowed a maximum CA production of 434 mg\(\cdot\)L\({}^{-1}\)[194]. The authors emphasized that this technology constitutes a low-cost platform to simultaneously produce and recover CA with high yields. Similarly, [PERSON] and [PERSON] employed extractive fermentation using IRA 400 ion-exchange resin, obtaining a CA recovery of 78%; thus, increasing the cumulative CA concentration in 248% compared to the control without product removal [195]. The increase of CA productivity when it is adsorbed from the fermentation broth supports the hypothesis that high CA concentration may inhibit the antibiotic biosynthesis. A different approach considers the use of aqueous two-phase micellar systems (ATPMS).