Top

Published in:

2015 | OriginalPaper | Chapter

16. Dynamic Enzymatic Kinetic Resolution of NSAIDS

Authors : A. H. Kamaruddin, M. H. Uzir, F. N. Gonawan, S. Y. Lau

Published in: Advances in Bioprocess Technology

Publisher: Springer International Publishing

Activate our intelligent search to find suitable subject content or patents.

search-config

AI-assisted search

Off

Abstract

The optical purity of non-steriodal anti-inflammatory drugs (NSAIDs) is one of the concerns in pharmaceutical industries, since the enantiomers demonstrate distinct physical and chemical characters. The production of single enantiomer of NSAIDs through dynamic enzymatic kinetic resolution (DEKR) has been pinpointed as among the promising approach developed in recent years. The substrate conversion and product enantioselectivity could be improved as compared to the conventional kinetic resolution. A combination of enzymatic kinetic resolution (EKR) and base-catalyzed racemization process can guarantee racemic substrate conversion of more than 80 %. The utilization of hollow-fiber membrane as enzyme-mediated reactor significantly improves the DEKR operation. This chapter describes the DEKR of a racemic ibuprofen in enzymatic membrane reactor (EMR), which system has been intensively investigated. From the experimental work, high conversion of the substrate (>90 %) and opticaly pure product (ee _P > 95 %) have been obtained. The kinetic model was integrated with that of the mass transfer in the cylindrical hollow-fiber module in order to simulating the entire system by the interaction between the EKR and racemization reaction. The product ((S)-ibuprofen acid) was crystallized and the preliminary toxicity studies were carried out. In conclusion, DEKR of NSAIDs is a promising technology for the production a single enantiomer of NSAIDs.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

über 102.000 Bücher
über 537 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Finance + Banking
Management + Führung
Marketing + Vertrieb
Maschinenbau + Werkstoffe
Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

inform now

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

über 67.000 Bücher
über 390 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Maschinenbau + Werkstoffe

Jetzt Wissensvorsprung sichern!

inform now

previous chapter Thermochemical Processing of Biomass

next chapter Catgut Waste Utilization for Protease Production Using Bacillus subtilis

Ansari, S. A., & Husain, Q. (2012). Potential applications of enzymes immobilized on/in nano materials: A review. Biotechnology Advances, 30(3), 512–523. doi:10.1016/j.biotechadv.2011.09.005.CrossRef

Ariëns, E. J. (1991). Racemic therapeutics – Ethical and regulatory aspects. European Journal of Clinical Pharmacology, 41(2), 89–93. doi:10.1007/bf00265897.CrossRef

Battistel, E., Bianchi, D., Cesti, P., & Pina, C. (1991). Enzymatic resolution of (S)-(+)-naproxen in a continuous reactor. Biotechnology and Bioengineering, 38(6), 659–664. doi:10.1002/bit.260380611.CrossRef

Bhandarkar, S. V., & Neau, S. H. (2000). Lipase-catalyzed enantioselective esterification of flurbiprofen with n-butanol. Electronic Journal of Biotechnology, 3(3), 1–7. doi:10.2225/vol3-issue3-fulltext-3.

Brady, D., & Jordaan, J. (2009). Advances in enzyme immobilisation. Biotechnology Letters, 31(11), 1639–1650. doi:10.1007/s10529-009-0076-4.CrossRef

Brady, D., Steenkamp, L., Skein, E., Chaplin, J. A., & Reddy, S. (2004). Optimisation of the enantioselective biocatalytic hydrolysis of naproxen ethyl ester using ChiroCLEC-CR. Enzyme and Microbial Technology, 34(3–4), 283–291. doi:10.1016/j.enzmictec.2003.11.002.CrossRef

Carnell, A. (1999). Stereoinversions using microbial redox-reactions. In K. Faber (Ed.), Biotransformations (Advances in Biochemical Engineering/Biotechnology, Vol. 63, pp. 57–72). Berlin: Springer. 10.1007/3-540-69791-8_3.CrossRef

Chang, C.-S., & Tsai, S.-W. (1997). A facile enzymatic process for the preparation of (s)-Naproxen ester prodrug in organic solvents. Enzyme and Microbial Technology, 20(8), 635–639. doi:10.1016/S0141-0229(96)00222-0.CrossRef

Chang, C.-S., Tsai, S.-W., & Lin, C.-N. (1998). Enzymatic resolution of (RS)-2-arylpropionic acid thioesters by Candida rugosa lipase-catalyzed thiotransesterification or hydrolysis in organic solvents. Tetrahedron: Asymmetry, 9(16), 2799–2807. doi:10.1016/S0957-4166(98)00296-1.CrossRef

Chen, C.-C., & Tsai, S.-W. (2005). Carica papaya lipase: A novel biocatalyst for the enantioselective hydrolysis of (R, S)-naproxen 2,2,2-trifluoroethyl ester. Enzyme and Microbial Technology, 36(1), 127–132. doi:10.1016/j.enzmictec.2004.07.004.CrossRef

Contesini, F. J., Lopes, D. B., Macedo, G. A., Nascimento, M. G., & Carvalho, P. O. (2010). Aspergillus sp. lipase: Potential biocatalyst for industrial use. Journal of Molecular Catalysis B: Enzymatic, 67(3–4), 163–171. doi:10.1016/j.molcatb.2010.07.021.CrossRef

Ducret, A., Trani, M., & Lortie, R. (1998). Lipase-catalyzed enantioselective esterification of ibuprofen in organic solvents under controlled water activity. Enzyme and Microbial Technology, 22(4), 212–216. doi:10.1016/S0141-0229(97)00180-4.CrossRef

Ebbers, E. J., Ariaans, G. J. A., Houbiers, J. P. M., Bruggink, A., & Zwanenburg, B. (1997). Controlled racemization of optically active organic compounds: Prospects for asymmetric transformation. Tetrahedron, 53(28), 9417–9476. doi:10.1016/S0040-4020(97)00324-4.CrossRef

Effenberger, F., Graef, B. W., & Oßwald, S. (1997). Preparation of (S)-naproxen by enantioselective hydrolysis of racemic naproxen amide with resting cells of Rhodococcus erythropolis MP50 in organic solvents. Tetrahedron: Asymmetry, 8(16), 2749–2755. doi:10.1016/S0957-4166(97)00335-2.CrossRef

Fazlena, H. (2005). Chemoenzymatic dynamic kinetic resolution of ethoxyethyl ibuprofen ester. Penang: Universiti Sains malaysia.

Fazlena, H., Kamaruddin, A. H., & Zulkali, M. M. D. (2006). Dynamic kinetic resolution: alternative approach in optimizing S-ibuprofen production. Bioprocess and Biosystems Engineering, 28(4), 227–233. doi:10.1007/s00449-005-0024-1.CrossRef

Fu, B., & Vasudevan, P. T. (2010). Effect of solvent − Co-solvent mixtures on lipase-catalyzed transesterification of canola oil. Energy & Fuels, 24(9), 4646–4651. doi:10.1021/ef901176h.CrossRef

Ghanem, A., Aboul-Enein, M. N., El-Azzouny, A., & El-Behairy, M. F. (2010). Lipase-mediated enantioselective kinetic resolution of racemic acidic drugs in non-standard organic solvents: Direct chiral liquid chromatography monitoring and accurate determination of the enantiomeric excesses. Journal of Chromatography A, 1217(7), 1063–1074. doi:10.1016/j.chroma.2009.10.080.CrossRef

Ghanem, A. (2007). Trends in lipase-catalyzed asymmetric access to enantiomerically pure/enriched compounds. Tetrahedron, 63(8), 1721–1754. doi:10.1016/j.tet.2006.09.110.CrossRef

Gonawan, F. N., Sie Yon, L., Kamaruddin, A. H., & Uzir, M. H. (2013a). Rapid base-catalyzed racemization of (R)-ibuprofen ester in isooctane–dimethyl sulfoxide medium with improved kinetic model. Industrial & Engineering Chemistry Research, 53(2), 635–642. doi:10.1021/ie403070u.CrossRef

Gonawan, F. N., Yon, L. S., Kamaruddin, A. H., & Uzir, M. H. (2013b). Effect of co-solvent addition on the reaction kinetics of the lipase-catalyzed resolution of ibuprofen ester. Journal of Chemical Technology & Biotechnology, 88(4), 672–679. doi:10.1002/jctb.3885.CrossRef

Gyo Lee, E., Soon Won, H., & Hyun Chung, B. (2001). Enantioselective hydrolysis of racemic naproxen methyl ester by two-step acetone-treated Candida rugosa lipase. Process Biochemistry, 37(3), 293–298. doi:10.1016/S0032-9592(01)00213-8.CrossRef

Hu, Y., Wang, Y., Luo, G., & Dai, Y. (2008). Modeling of a biphasic membrane reactor catalyzed by lipase immobilized in a hydrophilic/hydrophobic composite membrane. Journal of Membrane Science, 308(1–2), 242–249. doi:10.1016/j.memsci.2007.09.064.CrossRef

Ikeda, Y., & Kurokawa, Y. (2002). Enantioselective esterification of racemic ibuprofen in isooctane by immobilized lipase on cellulose acetate-titanium iso-propoxide gel fiber. Journal of Bioscience and Bioengineering, 93(1), 98–100. doi:10.1016/S1389-1723(02)80062-7.CrossRef

Ito, T., Ando, H., & Handa, H. (2011). Teratogenic effects of thalidomide: molecular mechanisms. Cellular and Molecular Life Sciences, 68(9), 1569–1579. doi:10.1007/s00018-010-0619-9.CrossRef

Johnson, A., Zawadzka, A., Deobald, L., Crawford, R., & Paszczynski, A. (2008). Novel method for immobilization of enzymes to magnetic nanoparticles. Journal of Nanoparticle Research, 10(6), 1009–1025. doi:10.1007/s11051-007-9332-5.CrossRef

Jin, J. N., Lee, S. H., & Lee, S. B. (2003). Enzymatic production of enantiopure ketoprofen in a solvent-free two-phase system. Journal of Molecular Catalysis B: Enzymatic, 26(3–6), 209–216. doi:10.1016/j.molcatb.2003.06.004.CrossRef

Kin, M. G., & Lee, S. B. (1996). Enzymatic resolution of racemic ibuprofen by lipase-catalyzed esterification reaction: Effects of water content and solid supports. Journal of Fermentation and Bioengineering, 81(3), 269–271. doi:10.1016/0922-338X(96)82221-5.CrossRef

Kim, M. G., Lee, E. G., & Chung, B. H. (2000). Improved enantioselectivity of Candida rugosa lipase towards ketoprofen ethyl ester by a simple two-step treatment. Process Biochemistry, 35(9), 977–982. doi:10.1016/S0032-9592(00)00129-1.CrossRef

Knoche, B., & Blaschke, G. (1994). Investigations on the in vitro racemization of thalidomide by high-performance liquid chromatography. Journal of Chromatography A, 666(1–2), 235–240. doi:10.1016/0021-9673(94)80385-4.CrossRef

Long, W. S., Bhatia, S., & Kamaruddin, A. (2003). Modeling and simulation of enzymatic membrane reactor for kinetic resolution of ibuprofen ester. Journal of Membrane Science, 219(1–2), 69–88. doi:10.1016/S0376-7388(03)00181-9.CrossRef

Long, W. S., Kamaruddin, A., & Bhatia, S. (2005). Chiral resolution of racemic ibuprofen ester in an enzymatic membrane reactor. Journal of Membrane Science, 247(1–2), 185–200. doi:10.1016/j.memsci.2004.09.019.CrossRef

Lau, S. Y., Gonawan, F. N., Bhatia, S., Kamaruddin, A. H., & Uzir, M. H. (2011). Conceptual design and simulation of a plant for the production of high purity (S)-ibuprofen acid using innovative enzymatic membrane technology. Chemical Engineering Journal, 166(2), 726–737. doi:10.1016/j.cej.2010.11.072.CrossRef

Lau, S. Y. (2013). Dynamic kinetic resolution of (R, S)-ibuprofen ester in an enzymatic hollow fiber membrane reactor system: Process design, modeling and simulation studies. Penang: Universiti Sains Malaysia.

Lau, S. Y., Uzir, M. H., Kamaruddin, A. H., & Bhatia, S. (2010). Lipase-catalyzed dynamic kinetic resolution of racemic ibuprofen ester via hollow fiber membrane reactor: Modeling and simulation. Journal of Membrane Science, 357(1–2), 109–121. doi:10.1016/j.memsci.2010.04.008.CrossRef

Lee, E. (2008). Epoxide hydrolase-mediated enantioconvergent bioconversions to prepare chiral epoxides and alcohols. Biotechnology Letters, 30(9), 1509–1514. doi:10.1007/s10529-008-9727-0.CrossRef

Liu, Y.-Y., Xu, J.-H., Wu, H.-Y., & Shen, D. (2004). Integration of purification with immobilization of Candida rugosa lipase for kinetic resolution of racemic ketoprofen. Journal of Biotechnology, 110(2), 209–217. doi:10.1016/j.jbiotec.2004.02.008.CrossRef

Litalien, C., & Jacqz-Aigrain, E. (2001). Risks and benefits of nonsteroidal anti-inflammatory drugs in children: A comparison with paracetamol. Paediatric Drugs, 3(11), 817–858. doi:10.2165/00128072-200103110-00004.CrossRef

Madhav, M. V., & Ching, C. B. (2001). Study on the enzymatic hydrolysis of racemic methyl ibuprofen ester. Journal of Chemical Technology & Biotechnology, 76(9), 941–948. doi:10.1002/jctb.466.CrossRef

Martín-Matute, B., & Bäckvall, J.-E. (2007). Dynamic kinetic resolution catalyzed by enzymes and metals. Current Opinion in Chemical Biology, 11(2), 226–232. doi:10.1016/j.cbpa.2007.01.724.CrossRef

Mak, X. Y., Laurino, P., & Seeberger, P. H. (2009). Asymmetric reactions in continuous flow. Beilstein Journal of Organic Chemistry, 5, 19. doi:10.3762/bjoc.5.19.CrossRef

Mehvar, R., & Brocks, D. R. (2001). Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans. Journal of Pharmacy and Pharmaceutical Sciences, 4(2), 185–200.

Morrone, R., Nicolosi, G., Patti, A., & Piattelli, M. (1995). Resolution of racemic flurbiprofen by lipase-mediated esterification in organic solvent. Tetrahedron: Asymmetry, 6(7), 1773–1778. doi:10.1016/0957-4166(95)00223-C.CrossRef

Muralidhar, R. V., Marchant, R., & Nigam, P. (2001). Lipases in racemic resolutions. Journal of Chemical Technology and Biotechnology, 76(1), 3–8. 10.1002/1097-4660(200101)76:1<3::AID-JCTB336>3.0.CO;2-8.CrossRef

Mustranta, A. (1992). Use of lipases in the resolution of racemic ibuprofen. Applied Microbiology and Biotechnology, 38(1), 61–66. doi:10.1007/bf00169420.CrossRef

Nagy, E., & Kulcsár, E. (2009). Mass transport through biocatalytic membrane reactor. Desalination, 245(1–3), 422–436. doi:10.1016/j.desal.2009.02.005.CrossRef

Patel, R. N. (2002). Microbial/enzymatic synthesis of chiral intermediates for pharmaceuticals. Enzyme and Microbial Technology, 31(6), 804–826. doi:10.1016/S0141-0229(02)00186-2.CrossRef

Patel, R. N. (Ed.). (2006). Biocatalysis in the pharmaceutical and biotechnology industries. A biocatalysis for synthesis for chiral pharmaceutical intermediates (1st ed.). New York, NY: CRC Press.

Perry, R. H., & Green, D. W. (1997). Perry’s chemical engineers’ handbook. Heat and mass transfer (7th ed.). New York, NY: Mc-Graw Hill.

Pollard, D. J., & Woodley, J. M. (2007). Biocatalysis for pharmaceutical intermediates: The future is now. Trends in Biotechnology, 25(2), 66–73. doi:10.1016/j.tibtech.2006.12.005.CrossRef

Rios, G. M., Belleville, M. P., Paolucci, D., & Sanchez, J. (2004). Progress in enzymatic membrane reactors – A review. Journal of Membrane Science, 242(1–2), 189–196. doi:10.1016/j.memsci.2003.06.004.CrossRef

Rouhi, A. M. (2003). Chiral business. Chemical and Engineering News Archive, 81(18), 45–61. doi:10.1021/cen-v081n018.p045.CrossRef

Schulze, B., & Wubbolts, M. G. (1999). Biocatalysis for industrial production of fine chemicals. Current Opinion in Biotechnology, 10(6), 609–615. doi:10.1016/S0958-1669(99)00042-7.CrossRef

Shah, R. R., & Branch, S. K. (2003). Regulatory Requirements for the Development of Chirally Active Drugs. In M. Eichelbaum, B. Testa, & A. Somogyi (Eds.), Stereochemical aspects of drug action and disposition. Handbook of experimental pharmacology (Vol. 153, pp. 379–399). Berlin: Springer. doi:10.1007/978-3-642-55842-9_16.CrossRef

Sheldon, R. A. (1996). Chirotechnology: Designing economic chiral syntheses. Journal of Chemical Technology & Biotechnology, 67(1), 1–14. doi:10.1002/(sici)1097-4660(199609)67:1<1::aid-jctb531>3.0.co;2-l.CrossRef

Sheldon, R. A. (2007). Enzyme immobilization: The quest for optimum performance. Advanced Synthesis & Catalysis, 349(8-9), 1289–1307. doi:10.1002/adsc.200700082.CrossRef

Sie Yon, L., Gonawan, F. N., Kamaruddin, A. H., & Uzir, M. H. (2013). Enzymatic deracemization of (R, S)-ibuprofen ester via lipase-catalyzed membrane reactor. Industrial & Engineering Chemistry Research, 52(27), 9441–9453. doi:10.1021/ie400795j.CrossRef

Steinreiber, J., Faber, K., & Griengl, H. (2008). De-racemization of enantiomers versus de-epimerization of diastereomers—Classification of dynamic kinetic asymmetric transformations (DYKAT). Chemistry – A European Journal, 14(27), 8060–8072. doi:10.1002/chem.200701643.CrossRef

Stoschitzky, K., & Lindner, W. (1990). Lindner W (1990) [Specific and nonspecific effects of beta receptor blockers: stereoselectively different properties exemplified by (R)- and (S)-propranolol]. Wiener Medizinische Wochenschrift, 140(6-7), 156–162.

Tsai, S. W., & Huang, C. M. (1999). Enantioselective synthesis of (S)-suprofen ester prodrugs by lipase in cyclohexane. Enzyme and Microbial Technology, 25(8–9), 682–688. doi:10.1016/S0141-0229(99)00108-8.CrossRef

Wang, L. W., Cheng, Y. C., & Tsai, S. W. (2004). Process modeling of the lipase-catalyzed dynamic kinetic resolution of (R, S)-suprofen 2,2,2-trifluoroethyl thioester in a hollow-fiber membrane. Bioprocess and Biosystems Engineering, 27(1), 39–49. doi:10.1007/s00449-004-0379-8.CrossRef

Wang, S.-Z., Wu, J.-P., Xu, G., & Yang, L.-R. (2013). Chemo-enzymatic asymmetric synthesis of S-citalopram by lipase-catalyzed cyclic resolution and stereoinversion of quaternary stereogenic center. Bioprocess and Biosystems Engineering, 36(8), 1031–1037. doi:10.1007/s00449-012-0855-5.CrossRef

Ward, T. J., & Ward, K. D. (2011). Chiral separations: A review of current topics and trends. Analytical Chemistry, 84(2), 626–635. doi:10.1021/ac202892w.CrossRef

Wiberg, E., & Wiberg, N. (Eds.). (2001). Inorganic chemistry. Stereochemistry of molecules (35th ed.). Academic Press: Florida.

Xin, J.-Y., Li, S.-B., Chen, X.-H., Wang, L.-L., & Xu, Y. (2000). Improvement of the enantioselectivity of lipase-catalyzed naproxen ester hydrolysis in organic solvent. Enzyme and Microbial Technology, 26(2–4), 137–141. doi:10.1016/S0141-0229(99)00147-7.CrossRef

Xin, J.-Y., Li S-b, S., Xu, Y., & Chui, C.-g. (2001). Dynamic enzymatic resolution of Naproxen methyl ester in a membrane bioreactor. Journal of Chemical Technology & Biotechnology, 76(6), 579–585. doi:10.1002/jctb.413.CrossRef

Yuchun, X., Huizhou, L., & Jiayong, C. (2000). Kinetics of base catalyzed racemization of ibuprofen enantiomers. International Journal of Pharmaceutics, 196(1), 21–26. doi:10.1016/S0378-5173(99)00438-X.CrossRef

Title: Dynamic Enzymatic Kinetic Resolution of NSAIDS
Authors: A. H. Kamaruddin
M. H. Uzir
F. N. Gonawan
S. Y. Lau
Publisher: Springer International Publishing
Book: Advances in Bioprocess Technology
Print ISBN: 978-3-319-17914-8

Electronic ISBN: 978-3-319-17915-5

Copyright Year: 2015
DOI: https://doi.org/10.1007/978-3-319-17915-5_16