Penicillin production fermentation

For B.Pharmacy students

1. Penicillin Production Fermentation
By:
Vasundhara S. Kakade
Assistant Professor
Department of Pharmaceutics
NES Navsahyadri Institute of Pharmacy, Nasarapur Pune.

2. What is Fermentation…?
•The Breakdown of organic substrate by Living Organisms
in a proper time interval into a product is called as
Fermentation.

3. Penicillin.
•Penicillin is a Naturally occuring Antibiotic.
•It is obtained from a Fungus called Penicillium notatum &
P.chrysogenum.
•It was the first Antibiotic to be discovered.
•It was first discovered by Alexander Fleming in 1928.
Alexander
fleming
Penicillium Chrysogenum
mold

4. Penicillium
Chrysogenum
Penicillium
notatum
•It was the first Antibiotic to be produced on a Large scale.
General
structure

5. •It is active against many gram positive bacteria.
•It kills the Bacterias by interfering with the cell wall
synthesis of sensitive organisms.
•It is inactive against most Gram negative bacteria.
Mechanism of Action of Penicillin

6. Penicillin Production.
•Penicillin was first comercially produced by using Stationary
mat culture method.

•But this technique was having a lot of problems.

•There were many chances of contamination of broth
during its harvesting.
•Fermentation technique was developed & it is the most
promising for Commercial production.

•This tech is still applied and Practiced till date & takes place
using a Fermenter.

8. 1. Inoculum preparation
•Penicillium chrysegenous with high yielding capacity is
selected as strain .
•These desired strains are stored in condition
•Lyophilized or soil suspension formation.
1. Freeze dried
product suspend
in water
2. Added in
Nutrient media
incubated 4-6
days at 25o C
3. Added into seed
fermenter tank with
agitation aeration &
incubate for 48 Hrs.
•The resulted inoculum used for fermentation.

9. 2. Media Preparation
•The media is designed to provide the organism with
desired nutrients.

•The exact composition of the Penicillin media actually
used in industries are difficult to determine as these are
considered Company’s trade secrets.

•But it consist of precursor
Phenyl acetic acid = Penicillin G.
Phenoxy acetic acid = Penicillin V.

10. 3. Fermentation Process
•Inside the Production fermenter the actual penicillin
fermentation takes place.

•The Fermenter is Incubated at about 25oc to 26oc for
about 5 to 7 days at pH 7 to 7.4

•During the first 20 to 30 hours the utilization nitrogen from
lactic acid .Which cause deamination of Carb and Corn
steep takes place, change pH,due to this fungal growth
becomes thick & heavy.

•Penicillin yield during 48 to 96 hrs. is very low or nothing.
•The yield increases at the time of stress when nutrients
are very low.

11. •During this whole production, periodic samples are taken
from fermenter for the determination of penicillin yield
and contamination checks.

12. 4. Harvest & recovery
•After the completion of fermentation Media or the Broth
contains penicillin. This needs to be extracted through
separation as follows:
 First the broth is filtered or centrifuge .

13. Then penicillin extracted by maintaining pH,
temperature, sterility etc to maintain physical &
chemical stability.

Organic solvent like, amyl acetate or butyl acetate is
added to lower the pH of broth to 2.5 to 2.
Then this solvent treated with charcoal to remove
impurities.
Then charcoal is removed and penicillin is
crystallized & converted to its salt for stability &
solubility .

THANK YOU