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T.BARKATHUN
NISHA
R..LAANNSWICK
B.SURIYAKALA
BON
SECOURS
COLLEGE
FOR
WOMEN
THANJAVUR
CONTENTS INTRODUCTION
 HISTORY
 PROPERTIES
 BIOSYNTHESIS OF PENICILLIN
 MODE OF ACTION
 CLASSIFICATION OF PENICILLIN
 CULTURE METHODS
SURFACE CULTURE
SUBMERGED CULTURE
 PRODUCTION PROCESS
 UPSTREAM PROCESS
 MEDIA FORMULATION
 HEAT STERILISATION
 FERMENTATION
 SEED CULTURE
 FILTERATION
 ADDITION OF SOLVENTS
 CENTRIFUGAL EXTRACTION
• DOWNSTREAM PROCESS
 EXTRACTION
 FLUID BED DRYING
 STORAGE
 MARKETING
 ADVANTAGES
 DISADVANTAGES
 QUESTION TIME
 PENICILLIN MANUFACTURES &SUPPLIERS
 RESEARCH ON GOING
 CONCLUSION
INTRODUCTION
 Penicillin is a secondary metabolite produced by certain
bacteria, which is used an antibiotic .
 ‘Antibiotic’ literally means ‘against life’ – but antibiotics only
kill life that is harmful to living creatures , i.e. bacteria.
 A bacterial infection is caused by millions of tiny bacteria
that are trying to survive and in multiply the body . An
antibiotic attacks and kill these bacteria .
 Before the development of penicillin , many people suffered
and died from bacterial infections that are no longer
considered dangerous today .
PENICILLIUM
HISTORY
 1928 – ALEXANDER FLEMING
Bread mold (Penicillium notatum) on petridish
inhibited the growth of bacteria.
Mold juice kills the bacterial species Streptococcus ,
meningococcus, diphtheria bacillus.
1939 – FLOREY , Chain, and Associates
Began work on isolating and synthesizing large
amounts of penicillin.
1941 – introduced in antibacterial therapy
1944 – penicillin has been at
the disposal of all people
History
ALEXANDER FLEMING
PENICILLIN LOGO
PROPERTIES
 Optically active.
 Soluble in water.
 Acid resistant.
 Hydrolyzed by hot inorganic acid .
 Effective in treatment of respiratory track infection .
BIOSYNTHESIS OF PENICILLIN BY
Penicillium chrysogenum
MODE OF ACTION:
NAM-N ACETYL
MURAMIC ACID
NAG-N ACETYL
GLUCOSAMINE
Penicillin interfere linking of
peptidoglycon in bacteria
Cell wall without intact
peptidoglycon cross-links are
structurally weak
Here is an video showing the
activity of penicillin
CLASSIFICATION
Culture methods
 The fungus can be cultured in two methods ,namely
Surface culture method
 In surface culture method ,the fungus is cultured on
the surface of a liquid medium without agitation.
 Surface of the medium is inoculated with dry spores
to cover the surface uniformly.
 After an appropriate incubation period ,the penicillin
is extracted from the medium .
Submerged culture method
 In submerged culture method ,the fungus is grow in a
liquid medium which is vigorously aerated and
agitated.
 Medium is inoculated dry spores by, pellet inocula.
 It saves time in the production stage.
 After an appropriate incubation period ,the penicillin
is separated from the medium .
PRODUCTION OF PENICILLIN
 The industrial production of penicillin as broadly
classified in to two processes namely ,
Upstream processing
 Upstream processing encompasses any technology
that leads to the synthesis of a product.
 Upstream includes
Downstream processing
 The extraction and purification of a biotechnological
product from fermentation is referred to as
downstream processing.
Production process
Media formulation
 Ph6.5
 Temperature 20-24c
 Oxygen
 Nitrogen (corn steep liquor 8.5%)
 Glucose 1% (preferred for penicillium notatum)
 80% ethanol
 Phenyl acetic acid
 Probenecid
 Lactose 1%
 Calcium carbonate 1%
 Sodium hydrogen phosphate 0.4%
 Antifoaming agent : Vegetable oil
Heat sterilization
121 degree celcius at 30 psi (pounds per square inch).
For high temperature short time for sterilization is
used to minimize the degradation
of certain components of media.
FERMENTATION
 Usually done by fed-batch mode
 High amount of glucose result in low yield of
Penicillin.
 Temperature : 20 to 24 c
 pH : 6.0 to 6.5 units
 Pressure : 1.02 atmosphere (higher than atmospheric
pressure to prevent contamination )
Fermentation:
• Sparging of air provided for
providing sufficient oxygen
required for cell viability.
IMPELLER:
•Rotor used to increase the
pressure and flow of fluid.
• Used to mix culture throughout
the medium
• Fungal cells are hardy
• Hence handled at rotation
speed around 200rpm
FERMENTORS
SEED CULTURE:
o First done in lab by adding penicillium spores to the
liquid medium.
o After growth , inoculated into the fermentor.
o In some cases spores are directly inoculated into the
fermentor.
Spore: produced during stress condition
FILTERATION:
 Rotary vaccum filter is used for large scale
production.
 To remove biomass such as fungus, other
impurities from the medium.
Phosphoric acid is added pH become 8.5
This can leads to the loss of penicillin activity.
Thus pH is maintained at 6.0 to 6.5. ROTARY VACCUM FILTER
Addition of solvents :
 AMYL ACETATE or BUTYL ACETATE is added to
dissolve penicillin in filtrate.
 Now, penicillin is present in the form of solution.
 Other solids are considered as wastes.
CENTRIFUGAL EXTRACTION:
 Tubular bowl or chamber bowl centrifuge is used.
 To separate solid waste from liquid component which
contains the penicillin.
 Supernatent is transferred to downstream process.
EXTRACTION
PENICILLIN + ACETATE SOLUTION
1.Phosphate buffer
2.Chloroform solution
3.Again phosphate buffer
4.Ether solution
Mixed with
 Penicillin is present in high concentration in ether
solution
Solids are easily removed by basket centrifugation.
Penicillin salt is in stable powdered form at room
temperature .
Basket centrifuge
Fluid bed drying:
 To remove the moisture present in the penicillin salt.
 Hot gas is pumped from the base of the chamber.
 Powdered salt is contained in a vaccum chamber.
 Results in dried form of penicillin.
Storage:
Stored in containers in dried environment.
Then packaged into
Liquid penicillin
Penicillin in pills
process
rotating filter
filtrate fungal cells
Dissolve in butyl acetate animal feed
Potassium ions added to
Precipitate salt of penicillin
Wash, filter and dry
99.55% pure penicillin
Uses of penicillin:
 Skin and soft tissue infections.
 Diphtheria , tetanus
 Intra abdominal infection
 Ear, lung , infections
 Respiratory tract infection
 Urinary tract infection
 Dental infection
 Syphilis , gonorrhea
 Streptococcol infection
ADVANTAGES
 Have excellent tissue penetration .
 Bactericidal against sensitive strains.
 Relatively nontoxic.
 Efficacious in the treatment of infections.
 Inexpensive in comparision with other antibiotics.
 Newer penicillin’s are resistant to stomach acid , such
as penicillin V or a broader spectrum ,such as
ampicillin and amoxicillin.
DISADVANTAGES
 Acid liability – most of these drugs are destroyed by
gastric acid.
 Lack of activity against most gram negative organisms.
 Short duration of action.
 Many patients experience GI upset.
 Painful if given intramuscularly.
QUESTION TIME
Why penicillin injection is used ?
Penicillins are a certain collection of antibiotics
that eliminate infection causing bacteria.
They are used in the treatment or prevention of
many different bacterial infections ,usually caused by
gram positive organisms.
What are the side effects of penicillin?
 fast or irregular breathing
 fever
 joint pain
 puffiness or swelling around the face
 red ,scaly skin
 shortness of breath
 skin rash, hives ,itching
What formulations of penicillin antibiotics are
available ?
 tablets
 capsules
 powder for oral suspension
 powder for injection
Are penicillin antibiotics safe to take
during in pregnancy?
Penicillin antibiotics are considered safe to
use during pregnancy.
What happens if overdose?
 Seek emergency medical attention .
 Symptoms :
 Skin rash
 Less urination
 Seizure (black out or convulsions
i.e.muscle contraction and relaxation )
What happens if you miss a dose ?
 Take the missed dose as soon as you remember.
 Do not take extra medicine.
Penicillin manufactures &suppliers
 Servo care life sciences pvt.ltd.
(Chandigarh, India)
 Karan health care private limited
(New Delhi, India)
 Alchemy medicine pvt.ltd.
(Gurgaon,India)
 Medicare remedies private limited
(Navy Mumbai, India)
RESEARCH NEWS
 Research supports re-introduction of penicillin type
antibiotics as adjunct therapeutic for MRSA infections.
 MRSA Methicillin resistant Staphylococcuc aureus.
 Resistant to antibiotics used to treat staphylococcus
infection.
 Australia Menzies school of Health Research showed ,
Precautions :
 Patients with a history of penicillin allergy should be
skin tested. more than 80% of patients with a history
of penicillin allergy will have negative skin tests.
 No life threatening false negative reactions have been
reported.
SUMMARY
 Penicillin is isolated from the fungus Penicillium sp.
 It is used as antibiotic all over the world .
 Its act by interfering the cell wall linkage of bacteria.
 The production process involves upstream and
downstream process.
 Upstream includes exploration, development and
production.
 Downstream include extraction, purification, marketing of
penicillin.
 Penicillin cure many gram positive bacterial diseases such
as syphilis, gonorrhea, respiratory tract infection, etc.
 Penicillin is known as “WONDER DRUG”
Any questions?

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penicillin

  • 2. CONTENTS INTRODUCTION  HISTORY  PROPERTIES  BIOSYNTHESIS OF PENICILLIN  MODE OF ACTION  CLASSIFICATION OF PENICILLIN  CULTURE METHODS SURFACE CULTURE SUBMERGED CULTURE  PRODUCTION PROCESS  UPSTREAM PROCESS  MEDIA FORMULATION  HEAT STERILISATION  FERMENTATION  SEED CULTURE  FILTERATION  ADDITION OF SOLVENTS  CENTRIFUGAL EXTRACTION • DOWNSTREAM PROCESS  EXTRACTION  FLUID BED DRYING  STORAGE  MARKETING  ADVANTAGES  DISADVANTAGES  QUESTION TIME  PENICILLIN MANUFACTURES &SUPPLIERS  RESEARCH ON GOING  CONCLUSION
  • 3. INTRODUCTION  Penicillin is a secondary metabolite produced by certain bacteria, which is used an antibiotic .  ‘Antibiotic’ literally means ‘against life’ – but antibiotics only kill life that is harmful to living creatures , i.e. bacteria.  A bacterial infection is caused by millions of tiny bacteria that are trying to survive and in multiply the body . An antibiotic attacks and kill these bacteria .  Before the development of penicillin , many people suffered and died from bacterial infections that are no longer considered dangerous today .
  • 5. HISTORY  1928 – ALEXANDER FLEMING Bread mold (Penicillium notatum) on petridish inhibited the growth of bacteria. Mold juice kills the bacterial species Streptococcus , meningococcus, diphtheria bacillus. 1939 – FLOREY , Chain, and Associates Began work on isolating and synthesizing large amounts of penicillin. 1941 – introduced in antibacterial therapy 1944 – penicillin has been at the disposal of all people
  • 8. PROPERTIES  Optically active.  Soluble in water.  Acid resistant.  Hydrolyzed by hot inorganic acid .  Effective in treatment of respiratory track infection .
  • 9. BIOSYNTHESIS OF PENICILLIN BY Penicillium chrysogenum
  • 10. MODE OF ACTION: NAM-N ACETYL MURAMIC ACID NAG-N ACETYL GLUCOSAMINE Penicillin interfere linking of peptidoglycon in bacteria Cell wall without intact peptidoglycon cross-links are structurally weak
  • 11. Here is an video showing the activity of penicillin
  • 13. Culture methods  The fungus can be cultured in two methods ,namely
  • 14. Surface culture method  In surface culture method ,the fungus is cultured on the surface of a liquid medium without agitation.  Surface of the medium is inoculated with dry spores to cover the surface uniformly.  After an appropriate incubation period ,the penicillin is extracted from the medium .
  • 15. Submerged culture method  In submerged culture method ,the fungus is grow in a liquid medium which is vigorously aerated and agitated.  Medium is inoculated dry spores by, pellet inocula.  It saves time in the production stage.  After an appropriate incubation period ,the penicillin is separated from the medium .
  • 16. PRODUCTION OF PENICILLIN  The industrial production of penicillin as broadly classified in to two processes namely ,
  • 17. Upstream processing  Upstream processing encompasses any technology that leads to the synthesis of a product.  Upstream includes
  • 18. Downstream processing  The extraction and purification of a biotechnological product from fermentation is referred to as downstream processing.
  • 20. Media formulation  Ph6.5  Temperature 20-24c  Oxygen  Nitrogen (corn steep liquor 8.5%)  Glucose 1% (preferred for penicillium notatum)  80% ethanol  Phenyl acetic acid  Probenecid
  • 21.  Lactose 1%  Calcium carbonate 1%  Sodium hydrogen phosphate 0.4%  Antifoaming agent : Vegetable oil
  • 22. Heat sterilization 121 degree celcius at 30 psi (pounds per square inch). For high temperature short time for sterilization is used to minimize the degradation of certain components of media.
  • 23. FERMENTATION  Usually done by fed-batch mode  High amount of glucose result in low yield of Penicillin.  Temperature : 20 to 24 c  pH : 6.0 to 6.5 units  Pressure : 1.02 atmosphere (higher than atmospheric pressure to prevent contamination )
  • 24. Fermentation: • Sparging of air provided for providing sufficient oxygen required for cell viability. IMPELLER: •Rotor used to increase the pressure and flow of fluid. • Used to mix culture throughout the medium • Fungal cells are hardy • Hence handled at rotation speed around 200rpm FERMENTORS
  • 25. SEED CULTURE: o First done in lab by adding penicillium spores to the liquid medium. o After growth , inoculated into the fermentor. o In some cases spores are directly inoculated into the fermentor. Spore: produced during stress condition
  • 26. FILTERATION:  Rotary vaccum filter is used for large scale production.  To remove biomass such as fungus, other impurities from the medium. Phosphoric acid is added pH become 8.5 This can leads to the loss of penicillin activity. Thus pH is maintained at 6.0 to 6.5. ROTARY VACCUM FILTER
  • 27. Addition of solvents :  AMYL ACETATE or BUTYL ACETATE is added to dissolve penicillin in filtrate.  Now, penicillin is present in the form of solution.  Other solids are considered as wastes.
  • 28. CENTRIFUGAL EXTRACTION:  Tubular bowl or chamber bowl centrifuge is used.  To separate solid waste from liquid component which contains the penicillin.  Supernatent is transferred to downstream process.
  • 29. EXTRACTION PENICILLIN + ACETATE SOLUTION 1.Phosphate buffer 2.Chloroform solution 3.Again phosphate buffer 4.Ether solution Mixed with
  • 30.  Penicillin is present in high concentration in ether solution Solids are easily removed by basket centrifugation. Penicillin salt is in stable powdered form at room temperature . Basket centrifuge
  • 31. Fluid bed drying:  To remove the moisture present in the penicillin salt.  Hot gas is pumped from the base of the chamber.  Powdered salt is contained in a vaccum chamber.  Results in dried form of penicillin.
  • 32. Storage: Stored in containers in dried environment. Then packaged into Liquid penicillin Penicillin in pills
  • 34. rotating filter filtrate fungal cells Dissolve in butyl acetate animal feed Potassium ions added to Precipitate salt of penicillin Wash, filter and dry 99.55% pure penicillin
  • 35. Uses of penicillin:  Skin and soft tissue infections.  Diphtheria , tetanus  Intra abdominal infection  Ear, lung , infections  Respiratory tract infection  Urinary tract infection  Dental infection  Syphilis , gonorrhea  Streptococcol infection
  • 36. ADVANTAGES  Have excellent tissue penetration .  Bactericidal against sensitive strains.  Relatively nontoxic.  Efficacious in the treatment of infections.  Inexpensive in comparision with other antibiotics.  Newer penicillin’s are resistant to stomach acid , such as penicillin V or a broader spectrum ,such as ampicillin and amoxicillin.
  • 37. DISADVANTAGES  Acid liability – most of these drugs are destroyed by gastric acid.  Lack of activity against most gram negative organisms.  Short duration of action.  Many patients experience GI upset.  Painful if given intramuscularly.
  • 38. QUESTION TIME Why penicillin injection is used ? Penicillins are a certain collection of antibiotics that eliminate infection causing bacteria. They are used in the treatment or prevention of many different bacterial infections ,usually caused by gram positive organisms.
  • 39. What are the side effects of penicillin?  fast or irregular breathing  fever  joint pain  puffiness or swelling around the face  red ,scaly skin  shortness of breath  skin rash, hives ,itching
  • 40. What formulations of penicillin antibiotics are available ?  tablets  capsules  powder for oral suspension  powder for injection
  • 41. Are penicillin antibiotics safe to take during in pregnancy? Penicillin antibiotics are considered safe to use during pregnancy.
  • 42. What happens if overdose?  Seek emergency medical attention .  Symptoms :  Skin rash  Less urination  Seizure (black out or convulsions i.e.muscle contraction and relaxation )
  • 43. What happens if you miss a dose ?  Take the missed dose as soon as you remember.  Do not take extra medicine.
  • 44. Penicillin manufactures &suppliers  Servo care life sciences pvt.ltd. (Chandigarh, India)  Karan health care private limited (New Delhi, India)  Alchemy medicine pvt.ltd. (Gurgaon,India)  Medicare remedies private limited (Navy Mumbai, India)
  • 45. RESEARCH NEWS  Research supports re-introduction of penicillin type antibiotics as adjunct therapeutic for MRSA infections.  MRSA Methicillin resistant Staphylococcuc aureus.  Resistant to antibiotics used to treat staphylococcus infection.  Australia Menzies school of Health Research showed ,
  • 46. Precautions :  Patients with a history of penicillin allergy should be skin tested. more than 80% of patients with a history of penicillin allergy will have negative skin tests.  No life threatening false negative reactions have been reported.
  • 47. SUMMARY  Penicillin is isolated from the fungus Penicillium sp.  It is used as antibiotic all over the world .  Its act by interfering the cell wall linkage of bacteria.  The production process involves upstream and downstream process.  Upstream includes exploration, development and production.  Downstream include extraction, purification, marketing of penicillin.  Penicillin cure many gram positive bacterial diseases such as syphilis, gonorrhea, respiratory tract infection, etc.  Penicillin is known as “WONDER DRUG”