Drugs
 A drug is defined as a chemical substance that is used as a medication for the diagnosis or treatment of a
disease.
 Drugs are chemical substances that affect or alter the physiology when taken into a living system. They can
either be natural or synthetic.
 Chemically, they are low atomic mass and molecular mass structures. When a drug is therapeutically active
and is used for the diagnosis, treatment or prevention of a disease, it is called medicine (legal drugs).
 They target the macromolecules inside the body and generate a biological response. Most of them interrupt
the nervous system (especially the brain) for the generation of a proper biological response. However, they
can be toxic in higher doses and generally referred to as lethal doses.
 Antibiotics are chemical substances produced by specific type of microorganisms which will inhibit growth
and even destroy body-harmful microorganisms
 Penicillin was the first of this group discovered in 1929 by Fleming in UK .
 He observed the inhibiting effect of penicillin mold on Staphylococcus aureus, a common infectious bacteria
 Fermentation process receiving only little competition from synthetic methods especially in producing
antibiotics because of following reasons
 Complex structures of antibiotics developed by fermentation, which are difficult to produce synthetically
 Cost of production of antibiotics by synthetic methods is very high compared to fermentation processes
 A few examples of drugs produced by fermentation under different conditions are
• Penicillin, terramycin, streptomycin, chloromycin, neomycin,
Variations in R and M
Changes of M in main ring will impart solubility and ingestion rate control:
• Direct rapid action injection:
M = Na or K
• Oral tablets:
M = K, Ca, Al
• Delayed action oil-base injection: impart limited water solubility
M = procaine or other derivative to
 Benzyl derivative and n-heptyl derivative penicillin are clinically most
desirable
 Complex synthesis by specific types of penicillium mold in fermentation broth
containing precursors
 Combination of specificity of mold and substrate composition produces a
certain type of penicillin
Raw materials : Most desirable fermentation base liquor is derived from maize or soyabeans
NOT REQUIRED. JUST FOR UNDERSTANDING
Keywords:
Mycelia: It is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae.
Spore: Spores are the main reproductive units for fungi and are usually single cells.
A spore is a cell that certain fungi, plants (moss, ferns), and bacteria produce.
Incolution: Injection or Microbiologists collect a small sample of microbes from a given source (we call this
small sample an "inoculum") and
place them into a medium that contains the nutrients needed for growth.
Precursur: a substance, cell, or cellular component from which another substance, cell, or cellular
component is formed
Strain: In biology, a strain is a genetic variant, a subtype or a culture within a biological species.
Fermentation broth: fermentation liquid or soup
Anti-foam agents works (used lard oil, octadecanol and silicones ): Maximum accumulation of penicillin.
Ease of extraction and purification of antibiotics.
Mold: is one of the structures certain fungi can form.
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• In biology, a substrate can be the surface on which an organism (eg: plant, fungus,
or animal) lives or the substance on which an enzyme can act.
• a substrate is the molecule upon which an enzyme or chemical reaction acts, while a
reagent is a substance added to initiate or test a chemical reaction.
1. In microbiology, an inoculum refers to the material used to initiate a
microbial culture, typically consisting of cells or spores introduced into a
growth medium
2. corn steep liquor (CSL), a by‐product of corn wet‐milling, is a valuable
nutrient‐rich medium used for cultivating microorganisms, especially in the
production of enzymes, antibiotics, and other fermentation products.
3. Fermentation broth" is a nutrient‐rich medium where microorganisms,
including molds, grow and produce substances, and a "precursor" refers to a
molecule that is converted into a final product during fermentation, with
molds playing a role in some fermentations.
Process description for production of penicillin by fermentation process
 In the manufacture of penicillin, fermentation is the preferred route. Penicillin production consists of three
stages. These are fermentation, extraction and purification of penicillin. In fermentation process the
fermentation substrate consists mainly of the sucrose found in corn steep liquor and lactose together with
minerals and mycelia are fed to the fermentation tank.
 The whole process is aerobic (it requires air). The fermentation is carried out over 4 or 5 days at 25-27°C. This
gives a yield of about 0.5% penicillin.
 The mycelium, the mold cells plus insoluble metabolites, is filtered off in a coated rotary drum filter. The filtrate
is adjusted the pH 2 with sulphuric acid. At this pH, the penicillin exists as an undissociated acid and it is
extracted in extraction process by adding organic solvents like butyl acetate or ketone; consequently, it is
soluble in organic solvents. After extraction the solution is decolourised and impurities are removed by
activated carbon.
 The penicillin is then precipitated by addition of inorganic solvent like solution of potassium acetate or Na
salt or KOH. The precipitated penicillin converts in to crystalized salts of penicillin. Then it is filtered and
dried and formed the solids of penicillin.
Molds reproduce by means of tiny spores; the spores are invisible to
the naked eye and float through outdoor and indoor air. Mold may
begin growing indoors when mold spores land on surfaces that are
wet.
In microbiology, molds are a type of fungus that reproduce through tiny,
airborne spores, which are like seeds for fungi, allowing them to spread
and colonize new areas.
Molds and Spores:
• Molds are fungi:
• Molds are a type of eukaryotic, multicellular microorganism that are
part of the fungal kingdom.
Reproduction through spores:
• Molds reproduce primarily through spores, which are microscopic,
lightweight cells that
• In microbiology, sterilization is the complete elimination of all
microorganisms, including both vegetative and spore forms, from a surface or
object, achieved through physical or chemical methods.
• A sterile surface/object is completely free of living microorganisms and
viruses.
TYPE II PENICILLIN
Extraction is done by H3PO4 followed by amyl acetate
Three stages
• Fermentation
• Extraction
• Purification.
Aerobic
Amyl acetate
solution
Extract
4-6 days
Na2PO4
Raffinate
Solvent
recycle
Solvent
recycle
Remove the salt
pH 7
Maintain pH 2 to 2.5
Maize liquor+ 4 to 5% solids with water+ 4-5% lactose and add nutrients
CaCO3 (pH 5 to 6) and alkali salt added and add
sterilizer
presurcer (phenyl acetic acid)
Nutrients such as magnesium,
zinc and/or sodium sulfate,
ammonium
acetate,
and
potassium dihydrogen sulfate
in amount of less than 0.2%.
Calcium carbonate is added
to adjust the pH to 5-6.
Major Engineering Problems.
 Design of 100-200 m³ fermenters to provide uniform and efficient air-liquid contact. Tanks
are pressurized to 1 atm. gage and air is added just underneath a high speed turbine agitator.
Foaming is avoided by addition of small quantities of antifoam agent such as octadecanol.
 Sterile operations as outlined in general discussion of fermentation engineering.
 Recovery of penicillin-solvent extraction method has replaced original activated carbon
adsorption-elution procedure.