(336h) Supported Liquid Membranes with Strip Dispersion Utilizing Aliquat 336 for the Recovery of Cephalexin From Aqueous Solutions

Cephalexin is an important and widely used semisynthetic cephalosporin. Cephalosprorins along with penicillins are β-lactam antibiotics, which account for the majority of the antibiotic world market. Cephalexin is traditionally produced by a ten step chemical synthesis. This process uses large amounts of organic solvents, and requires extensive cooling to low temperatures. An enzymatic synthesis for Cephalexin has been developed, and offers several advantages over the classical route. The enzymatic synthesis takes place in water and at room temperatures, thereby reducing energy use and solvent waste. The enzymatic process has been used in industrial production on a limited basis due to its difficult separation of Cephalexin from the starting products 7-ADCA, phenylglycine amide, and the side product phenylgyline. Liquid membranes, in particular supported liquid membranes (SLMs), are a promising solution to the separation. SLMs are not used commercially, as they are still plagued with problem of long term instability. SLM with strip dispersion has been a recent development to solve the issue of stability.

SLMs with strip dispersion are formed when an aqueous strip solution is dispersed in an organic membrane solution by a mixer, and passed on one side of a membrane support. When a microporous hydrophobic support is used, the organic phase of the dispersion becomes imbedded in the pores of the support, forming a stable SLM. Stability is maintained by having a constant supply of organic membrane solution to the pores. An aqueous feed solution is passed on the other side of the membrane support and the target species is extracted into the organic solution by a selective carrier. The target species is then stripped by the aqueous strip solution. For final recovery of the target species, the mixer is turned off and the dispersion quickly separates. The technology has potential for scale-up to the industrial scale, as commercial sized hollow fiber modules are widely available.

In this study, Cephalexin has been separated and concentrated from an aqueous solution using SLMs with strip dispersion. Key experimental parameters were studied. The organic membrane solution of the SLM consisted of Aliquat 336, Isopar L (isoparaffinic hydrocarbon solvent), and 1-decanol. The aqueous strip solution was composed of potassium chloride and citrate buffer. An enrichment factor of 3.2 was observed in the aqueous strip solution while achieving over 99% extraction and 96.2% total recovery. In this case, the aqueous feed solution of 5500 ppm (15 mM) was lowered to 30 ppm when using an organic membrane solution containing 2.5% Aliquat 336. The resulting overall mass transfer coefficient was 1.6 x 10-5 cm/sec. The mass flux of Cephalexin for this system was found to be independent of aqueous feed and strip dispersion flowrates, suggesting a major mass transfer resistance due to chemical reaction kinetics, which is supported by calculated individual mass transfer resistances. The pH of the aqueous strip phase was found to play a more significant role when trying to achieve higher enrichment ratios. It was observed that the highest stripping efficiency occurs when the pH of the aqueous strip phase is between the values of 5 and 6.

The carrier, Aliquat 336, can also extract other anions present in the feed solution, such as buffer ions. Three different methods of controlling the feed solution were investigated and their effect on Cephalexin extraction and recovery were analyzed. The three methods included a sodium carbonate-sodium bicarbonate buffer, monobasic sodium phosphate-dibasic sodium phosphate buffer, and continuous pH adjustment by sodium hydroxide. A sodium carbonate-sodium bicarbonate buffer as the feed solution resulted in the highest degrees of extraction and recovery of Cephalexin. This can be attributed to more co-extraction of phosphate and hydroxide ions compared to carbonate ions.