PROCESS DEVELOPMENT FOR SYNTHESIZING CEFPODOXIME PROXETIL
Cephalosporins are the highly used Broad spectrum antibiotics, belong to Î²-lactam class . It was discovered by Brotzu in fungus Cephalosporium Acremonium which produces a chemical which show antimicrobial activity. Abraham isolated the three types of cephalosporin antibiotics cephalosporin P, cephalosporin N, cephalosporin C.7-ACA is widely used as the substrate for synthesizing cephalosporin antibiotics. Modification of the 7-ACA side-chains resulted in the development of useful antibiotic agents, and the first agent is Cephalothin (cefalotin) was launched by. Eli Lilly Company in 1964. Cephalosporins resemble penicillinin that they have a Î²-lactam structure, but the five-memberthiazolidine ring characteristic of the penicillin is replacedby a six-member dihydrothiazine ring. The bactericidal action of beta lactam antibiotics is directly attributable to their ability to react with PBP's. The research work relates to an improved and cost effective process for the industrial manufacture of Cefpodoxime Proxetil. More specifically it relates to preparation of products of good quality with high yield and the products are removed and the same can be recycled using simple industrial and viable method. It can be possible with by using intermediate MAEM to synthesize Cefpodoxime proxetil. The drug is registered in USP and belongs to 3rd generation drug. There are many patents which gives the procedure of Synthesis of Cefpodoxime Proxetil. These synthesis procedures have taken as standard procedure for pursuing the project work. At present, MAEM is highly used intermediate to synthesis cephalosporin antibiotics. In this project work modification has done for synthesizingÂ of cephalosporin antibiotics by utilizing MAEM as intermediate and other chemicals like different Lewis acid, and solventÂ as alternateÂ of intermediate, chemicals and solvents which are given in patents to synthesize cephalosporin antibiotics .Resulting yield has improved via making small time synthesis reaction .This is helpful for the commercial purpose. The Reaction monitoringÂ were done by HPLC and identification of final product were done by MASS, I.R, NMR and then comparing with the well known literature. Recovery of the side product and byproduct (mercaptobenzothiazole) were achieved to allow a greener process and utilizes for synthesis of other familiar drugs.
2. Bayer T, Zhou W, Holzhauer K, Schiigerl K.: Investigations of cephalosporin C production in an airlift tower loop reactor. Appl Microbiol Biotechnol, 1989; 30:26_/33.
3. Heim J, Shen YQ, Wolfe S, Demain AL.: Regulation of isopenicillin N synthetase by carbon source during the fermentation of cephalosporium acremonium. Appl Microbiol Biotechnol 1984; 19:232;/6.
4. Dollery, C. (1999) Therapeutic drugs. Churchill. 3rded, Livingstone, Edinburgh.
5. Cephalosporins and Penicillin, Chemistry and Biology. Edited by E. H. Flynn, Academic Press, New York and London, 84, 1972.
6. Muthadi, F.J.; Hassan, M. A.; Florey, K.; (Ed.) Analytical Profiles of Drug Substances, Academy Press, New York, vol. 11, 1982, 159.
7. United States XXII Pharmacopeia, the United States Pharmacopeia Convention Inc., 12601 Twin brook Parkway, Rockville, MD 20852, 1990, 249-250.
8. Indian Pharmacopeia, Ministry of health and family welfare, Govt. of India, New Delhi; controller of publication, 2nd ed, 1996, A-740
9. Indian Pharmacopeia, Ministry of health and family welfare, Govt. of India, New Delhi; controller of publication, 4th ed, 1996, A-54
10. Camus F, Deslandes A, Harcouet L, Farinotti R. High-performance liquid chromatographic method for the determination of cefpodoxime levels in plasma and sinus mucosa. J Chromatogr B Biomed Appl. 1994 Jun 17;656(2):383â€“388.
11. R. P. Kotkar, A. A. Shirkhedkar and S. J. Surana, Int. J. Res. Pharm. Biomed. Sci., 3, 156-163 (2012).
12. Mills, T. J.; Roberson, C.; Instrumental Data for Drug Analysis, second ed., vol. 1, Elsevier, Amsterdam, 1987, 367.
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