CEPHALOSPORIN ANTIBIOTICS

Product Cefixime Trihydrate (Antibiotic)

Uses Bacterial Infection ( 3rd Generation Cephalosporins )
PROCESS CHEMISTRY (5 STAGE )

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 CEPHALOSPORIN ANTIBIOTICS
BRIEF PROCESS DESCRIPTION

Cefixime Manufacturing Process

Cefixime is a third generation cephalosporin antibiotic use for treatment of bacterial infection, it
consist of five steps comprises of witting reaction, deprotection, enzymatic hydrolysis,
condensation, basic hydrolysis, and crystallization
Stage-1: CFX-VI (GVNE)
GCLE is converted into its bromo derivative with sodium bromide, sodium iodide in DMF then it
undergoes wittig reaction in presence of triphenyl phosphine (TPP), caustic and formaldehyde
in MDC. MDC is distilled off under vacuum and product is isolated by adding methanol. Filtered,
washed with methanol and dried to give GVNE.
Stage-2: CFX-VIII (AVNA)
Deprotection of caboxylic acid and amino group is carried out with phenol and penicillin G
amidase enzyme respectively. Hydrolysed mass is treated with activated carbon than
crystallised by adjusting pH with dilute HCl to 4.0. 7-AVNA is filtered, washed with water and
dried.
Stage-3: Cefixime
7-Amino-3-vinyl-3-cephem-4-carboxylic acid (7-AVCA) is condensed with MICA Ester in
methanol / water mixture at pH 8.0 in presence of TEA. After completion of reaction, reaction
mixture is poured into water and its pH is adjusted. Mercaptobenzothiazol (MBT) is crystallised
out as by product. It is removed by filtration. To the filtrate, ethyl acetate, EDTA and water is
added and adjusted its pH with dilute HCl to get precursor of cefixime
i.e. methyl ester of cefixime.
Stage-4:
Methyl ester of cefixime is further subjected to basic hydrolysis using sodium hydroxide. The
product is crystallization by hydrochloric acid followed by centrifugation yields the Cefixime
which on further drying yields the Cefixime EP in the pure form.
Stage-5:
Final crystallization is carried out in the clean room area of class 100000 to avoid any cross
contamination.

Confidential PROCESS DETAILS Manoj Kumar Lal

 CEPHALOSPORIN ANTIBIOTICS
PROCESS FLOW DIAGRAM

Confidential PROCESS DETAILS Manoj Kumar Lal

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MATERIAL BALANCE

Material Balance for 01 MT

Sr. No. Raw Material MT Recovery & Consumption (MT)
Recycling (MT)
1 7-Phenyl acetamido 3- Chloromethyl 1.60
cephalosporanic acid p-methoxy
benzyl ester (GCLE)
2 Di Chloro methane (MDC) 13.68 13.3 0.41
3 Sodium Bromide 0.35
4 Sodium Iodide 0.05
5 Triphenylphosphine (TPP) 0.88
6 N, N-Dimethylformamide (DMF) 2.10 2.0 0.06
7 Formaldehyde 1.40 1.4 0.04
8 Sodium Hydroxide 0.19
9 Hydrochloric Acid (Commercial) 0.84
10 Phenol 3.28 3.2 0.10
11 n-Butyl acetate 20.38 19.8 0.61
12 Sodium bicarbonate 0.47
13 Sodium chloride 0.33
14 Penicillin-G amidase enzyme (wet) 0.83
15 Sodium Carbonate 0.25
16 EDTA di sodium 0.01
17 Methyl alcohol 8.50 8.2 0.26
18 Sulfuric acid 0.50
19 Acetone 18.00 17.5 0.54
20 MICA Ester 1.20
21 TEA 0.26 0.3 0.01
22 Ethyl Acetate 1.50 1.5 0.04
23 Sodium hydro sulphite 0.03
24 Activated carbon 0.30

Confidential PROCESS DETAILS Manoj Kumar Lal

 CEPHALOSPORIN ANTIBIOTICS

MARKET

TOTAL VOLUME (Kg) 799738

AVERAGE SELLING PRICE ( $/Kg) 158

EXPORT TO BANGALDESH, IRAN, MERCEDONIA,IRELAND ETC

Confidential PROCESS DETAILS Manoj Kumar Lal