(279a) Nanofiltration Process for the Separation of Cephalexin, 7-Adca and D-Phenylglycine Ternary System

Nanofiltration
process for the separation of cephalexin, 7-ADCA and D-phenylglycine ternary
system

Mengyuan
Wu, Xiaobin Jiang, Gaohong He*

State
Key Laboratory of Fine Chemicals, Research and Development Center of Membrane
Science and Technology, School of Chemical Engineering, Dalian University of
Technology, Dalian, P. R. China

*Corresponding
author: Email: hgaohong@dlut.edu.cn

Abstract

Cefalexin
is one of the most widely used cephalosporins antibiotics because of its broad
antimicrobial spectrum, high bioavailability and strong tolerance¹. The low yield
and difficult separation of Cefalexin have become the key factors restricting
its development. Traditionally, cefalexin was usually separated by complexation
method with a recovery of about 90%. However, the use of complexing agent
increased the separation cost and caused serious pollution to the environment. In
order to overcome the problems mentioned above to meet the requirements of
practical application, membrane separation technology has been applied to the
separation of cefalexin². Nanofiltration
membranes with high rejection to organic molecules with molecular weights of 150¨C2000
Da and multivalent ions, have attracted considerable attention in sea water
desalination, pharmaceutical and other applications³. Nanofiltration
membranes could effectively reject neutral and charged solutes through sieve effect and Donnan effect⁴. All the cefalexin and its pyrolysis
products 7-ADCA, D-phenylglycine, similar to amino acids, have zwitterionic
structures containing both amino and carboxyl groups, and their ionic states could
be changed with the change of solution PH (Figure 1)⁵. Similarly,
nanofiltration membranes could be charged negatively or positively by changing
the pH value of the solution to control the dissociation of surface functional
groups⁶. By
adjusting the pH value of the solution, the nanofiltration membrane and cefalexin/7-ADCA/D-phenylglycine
carried the same charge, so that the electrostatic repulsion between the membrane
and solute could be enhanced, and then the rejection of the membrane increased. In
the study, three kinds of polyamide nanofiltration membranes with different
interception molecular weights (DOW-NF90: MWCO=150Da;
GC-NF2001: MWCO=200Da; GC-NF5001: MWCO=500Da) were used to determine the rejection
of cefalexin, 7-ADCA and D-phenylglycine. As shown in Figure 2(a), with
the increase of the pore size of nanofiltration membrane, the rejection of D-phenylglycine decreased gradually, which was mainly
due to the fact that the molecular size of D-phenylglycine was smaller than the
pore sizes of all the nanofiltration membranes, so the sieve effect played the
dominant role. However, the rejections of Cefalexin and 7-ADCA were dependent
on the combination of sieve effect and Donnan effect. Compared with DOW-NF90
and GC-NF5001 membranes, GC-NF2001
membrane showed the highest rejection for 7-ADCA (77.85 %), which was due to
the higher negative charge of GC-NF2001 membrane than that of other two
membranes (Figure 2(b)). Meanwhile,
GC-NF2001 membrane also showed good separation efficiency for mixed solution of
7-ADCA (74.00 %) and D-phenylglycine (7.06 %), as shown in Figure 3. Nanofiltration membrane provides an idea
for the separation and purification of cefalexin and its
pyrolysis products.

Fig 1: (a) Cephalexin
ionization state, isoelectric point =4.72; (b) 7-ADCA ionization state, isoelectric
point =3.95; (c) D-phenylglycine
ionization state, isoelectric point =3.0;

Fig
2:
(a) Cefalexin, 7-ADCA and D-phenylglycine rejections
of commercial nanofiltration membranes; (b) Surface zeta potential of commercial nanofiltration membranes.

Fig
3:
(a)Spectral scans of Cephalexin; (b) Spectral scans of 7-ADCA; (c) Spectral scans
of D-phenylglycine;
(d) Spectral scans of mixed solution of 7-ADCA and D-phenylglycine

Acknowledgment

We acknowledge the financial
contribution from National Natural Science Foundation of China (Grant No.
21527812, 21676043, 21606035), the Fundamental Research Funds for the Central
Universities (DUT16TD19, DUT17ZD203) and MOST innovation team in key area (No.
2016RA4053).

References

1.         Maladkar
NK. Enzymatic production of cephalexin. Enzyme and Microbial Technology. 1994;
16(8): 715-718.

2.         Wang
KY, Chung T-S. The characterization of flat composite nanofiltration membranes
and their applications in the separation of Cephalexin. Journal of Membrane
Science. 2005; 247(1): 37-50.

3.         Shannon
MA, Bohn PW, Elimelech M, Georgiadis JG, Mariñas BJ, Mayes AM. Science and
technology for water purification in the coming decades. Nature. 2008; 452:
301.

4.         Lau
WJ, Gray S, Matsuura T, Emadzadeh D, Paul Chen J, Ismail AF. A review on
polyamide thin film nanocomposite (TFN) membranes: History, applications,
challenges and approaches. Water Research. 2015; 80: 306-324.

5.         Wang
KY, Xiao Y, Chung T-S. Chemically modified polybenzimidazole nanofiltration
membrane for the separation of electrolytes and cephalexin. Chemical
Engineering Science. 2006; 61(17): 5807-5817.

6.         Lalia
BS, Kochkodan V, Hashaikeh R, Hilal N. A review on membrane fabrication:
Structure, properties and performance relationship. Desalination. 2013; 326:
77-95.