Xavier University Ateneo de Cagayan

Corrales Avenue, Cagayan de Oro City, Philippines

Department of Chemical Engineering

Fermentation and
Pharmaceutical Industries

Caitor, Felizer
Conejar, Ian Glenn
Dano, Bryan Emmanuel
Gales, Angelyn
Rivas, Paulo
Tumala, John Paulo

November 20,2015

Fermentation Industries:

I.

Introduction.

Industrial fermentation is any microbial process controlled by humans that

produces useful products. The foundation of the of the scientific understanding of
fermentation, indeed of the action of all microorganisms, hence of their
economic control, rests firmly upon the genius of one man, Louis Pasteur.[1]
The production of lactic acid in 1880 was the beginning of industrial fermentation
to produce a useful product other than alcohol. During WW-1, Chaim Weizman
developed a fermentation process to convert corn to acetone and nbutanol.
During WW-2, the discovery of antibiotics, such as penicillin, set the stage for the
great technological advances in controlling microbiological processes that are
commonly used for today.
Uses.
Fermentation
under
controlled
conditions
involves
chemical
conversions[2]. Some of the more important processes are oxidation e.g. alcohol
to acetic acid and sucrose to citric acid: reduction, hydrolysis and esterification.
Many chemical reactions caused by microorganisms are very complex and
cannot be easily classified; so the concept of fermentation itself as a chemical
conversion has been developed. According to Silcox and Lee[3], the five basic
pre-req. of a good fermentation process are:
1.
2.
3.
4.
5.

A microorganism the forms desired end product.

Economical raw materials for substrate e.g. starch
Acceptable yields
Rapid fermentation
A product that is readily recovered and purified.

The yeasts, bacteria and molds employed in fermentation require specific

environments and food to ensure their activities. The concentration of sugar of
the sugar or other food affects the product. The most favourable temp. varies (540 deg. C) and the pH has great influence. Indeed, the bacteriologist has
developed acid-loving yeast, not liking acidic conditions, do not flourish. Some
microorganisms require air (aerobic) and other go through to their life process
without air (anaerobic). Certain anaerobes neither grow nor function in the
presence of air.
II.

Industrial Alcohol

Alcohol is second only to water in solvent value and is employed in nearly all
industries. In addition, it is the raw material for making of hundreds of chemicals
such as acetaldehyde, ethyl acetate, acetic acid, ethylene dibromide, glycols,
ethyl chloride, and all ethyl esters.
The principal reactions in
alcohol fermentation are:
Equations of
monosaccharide
production

Equations of fermentation

A small amount of glycerine is always found in alcohol fermentations. Toward the

end of a fermentation, the acidity and the glycerine increase. These are the
classic Gay-Lussac equations for alcohol formation. They are the principal
equations in an acid or low pH medium. When growing yeast for sale as such or
for inoculation, the yield for alcohol is lower, since it is partly changed to CO2
and H2O. This fermentation, like so many industrial reactions, is much more
involved than theses simple reactions indicate.
Energy requirements, unit operations, chemical conversions. Plant
procedures require steam heating for distillation, power for pumping, and water
for condensation, and occasionally for cooling during exothermic fermentation.
Several new methods of handling the various steps with the aim of improving
energy efficiency have been proposed. The manufacture of alcohol, as shown in
fig., can be broken down into the following steps.
Making of industrial alcohol. The flowchart in fig. shows the various
operations involved in changing corn to alcohol. The corn is degerminated,
dehulled and milled, either wet or dry. The milled corn is conveyed to the cooker.
The cooking is necessary to gelatinized the ground grain so that the barley malt
amylases can convert the starch to fermentable sugars. The cookers may be
batch or continuous and are operated under pressure. In the continuous process,
the grain is precooked to 1 to 5 minutes with water and stillage (the
dealcoholized, fermented beer that is discharged from the bottom of the beer
still). The mash is continuously fed to a steam heater that instantaneously raises
the temperature to 175C. The mashed is passed through a series of pipes and
discharged through a relief valve into a flash chamber. Time in the cooker is
about 1.5 min. and the pressure is maintained at 60 to 100 kPa gage. The
temperature of the mash drops about 60C in the flash chamber. The gelatinized
(cooked) grain mash is mixed with salty barley and water. The mix is pumped
through a pipeline (converter) for 2 min at 60C and then is sent to the
fermenters through pipe coolers. The starch is hydrolyzed to about 70% maltose
and 30% dextrins in the short time in the converter. Stillage (20% to 25%of the
final mash volume) from the beer still is added to the converted grain mash prior
to fermentation to lower the pH, furninsh nutrients for the yeast, and to add
buffering reaction. Meanwhile a charge of selected yeast (about 5% of the total
volume) has been growing in the yeast tub on a corn-barley malt mash which has
been previously sterilized under pressure and cooled. Bacteriologist have
cultivated a strain of yeast that thrives under acid conditions whereas wild
yeasts and bacteria do not. The mashed is pumped into the fermentor and the
yeast added as soon as 10% of the malt has been pumped. The initial pH is

adjusted to 4.8 to 5 with sulphuric acid and/ or stillage: As the reactions

indicates, fermentation is exothermic, so cooling maybe necessary to ensure that
maximum temperature does not exceed 32C. The time of the fermentation
cycle may vary from 40 to 72 h. The liquors in the fermentors after the action is
finished, are called beer. The alcohol is separated by distillation. The beer,
containing from 6.5 to 11% alcohol by volume, is pumped to the upper sections
of the beer still, after passing several heat exchangers. As the beer passes to the
column, it gradually loses its lighter boiling constituents. The liquid discharged
from the bottom of the still through a heat exchanger is known as stillage. It
carries proteins, residual sugars, and in some instances, vitamin products so it is
frequently evaporated and as used as a constituent of animal feed. The overhead
containing alcohol, water, and aldehydes passes through a heat exchanger to the
partial condenser or dephlegmator, which condenses sufficient of the vapors to
afford a reflux and also to strengthen the vapors that pass through the
condenser, where about 50% alcohol containing volatiles or aldehydes is
condensed. This condensate, frequently known as the high wines is conducted
into the aldehyde or heads, column from which the low boiling point impurities
are separated as an overhead. The effluent liquor from part way down the
aldehyde column flows into the rectifying column. In this 3 rd column the alcohol is
brought up to strength and finally purified in the following manner: The overhead
passing through a dephlegmator is partly condensed to keep the stronger alcohol
in this column and to provide reflux for the upper plates. The more volatile
products, which may still contain a trace of aldehydes. And of course alcohol, are
totally condensed and carried back to the upper part of the aldehyde still. Near
the top of the column 95 to 95.6% alcohol is taken off through a condenser for
storage and sale. Farther down the column, the higher the boiling fuel oils are
run off through a cooler and separator to a special still, where they are rectified
from any alcohol they may carry before being sold as an impure amyl alcohol for
solvent purposes. The bottom of this rectifying column discharges water.
Alcohol-water mixtures are rectified to increase the strength of the alcohol
component by virtue of the composition of the vapors being stronger in the more
volatile constituent than the liquid from which theses vapors arise. This shown
qualitatively by the curves in fig.2, where the composition of the vapour in
equilibrium with liquid is on the horizontal line. However, the alcohol cannot be
made stronger than 95.6% by rectification, because as can be seen from fig.
water forms a binary constant-boiling mixture of this composition which boils
slightly lower than absolute or anhydrous, alcohol. The principles shown here are
the basis of the strengthening of the more volatile constituent of any liquid
mixture by distillation.

Figure 1 Flowsheet for industrial alcohol

Figure 2 Temperature vs. Compostition of
vapour and liquid for alcohol-water at 101kPa

III. Acetone
Acetone (systematically named propanone) is the organic compound with the
formula (CH3)2CO. It is a colorless, volatile, flammable liquid, and is the simplest
ketone.
Acetone is miscible with water and serves as an important solvent in its own
right, typically for cleaning purposes in the laboratory. About 6.7 million tonnes
were produced worldwide in 2010, mainly for use as a solvent and production of
methyl methacrylate and bisphenol A. It is a common building block in organic
chemistry. Familiar household uses of acetone are as the active ingredient in nail
polish remover and as paint thinner.
During World War I, under the stimulus of the wartime demand for acetone for
the manufacture of smokeless powder (a substance essential for the British war
industry), Weizmann developed a process utilizing the fermentation of starch
containing grains to yield acetone and butyl alcohol which today is known as
Acetonebutanolethanol (ABE) fermentation.[1]
The process may be likened to how yeast ferments sugars to produce ethanol for
wine, beer, or fuel, but the organisms that carry out the ABE fermentation are
strictly anaerobic (obligate anaerobes). The ABE fermentation produces solvents
in a ratio of 3 parts acetone, 6 parts butanol to 1 part ethanol. It usually uses a
strain of bacteria from the Class Clostridia (Family Clostridiaceae). [2]

In 1960s, the ready availability of propylene led to routes based on cumene

peroxidation. The cumene route, in which the acetone is coproduced with phenol,
is the preferred technology because of its lower costs and nearly 83%-90% of
acetone is produced this way. The main process for manufacturing cumene

involves the reaction of propylene and benzene in the presence of phosphoric

acid-based catalysts or, more recently, zeolite catalysts. The cumene is oxidized
in the liquid phase to cumene hydroperoxide which is then cleaved in the
presence of sulphuric acid to phenol and acetone. About 0.62 tonnes of acetone
is produced with each tonne of phenol. [3]
Acetone is produced directly or indirectly from propylene. Approximately 83%90% of acetone is produced via the cumene process; as a result, acetone
production is tied to phenol production. In the cumene process, benzene is
alkylated with propylene to produce cumene, which is oxidized by air to produce
phenol and acetone:

IV. Acids
a. Acetic Acid
Commonly known as vinegar which came from the French word,
vinaigre which means, sour wine. Acetic acid is produced from the
oxidation of ethanol by the presence of bacteria genus of acetobacter.
The most used strain of acetobacter is the Acetobacter Aceti because it
is the most efficient of all it genus. The reaction is as follows:

2CH3CH2OH + O2 2CH3CHO + 2H2O

2CH3CHO + O2 2CH3COOH

There are 3 basic methods in producing acetic acid, these are Orleans
method, Trickling method and Submerged method.

I.

Orleans method
The first method was suggested by the Father of microbiology
himself: Louis Pasteur.
This method is to create and ideal condition for the bacteria to grow
as they would in nature. This start with the filling of the container up
to 2/3 full with wine, this is to allow air, which is needed for the
process. Then followed by the addition of inoculum of acetobacter,
then stored by 3-4 weeks at 80-85F, during this period of time, the
reaction discussed previously occurs in a slow manner. At some
point, a cellulosic material will form on top of the container, where
air is present, this is called the mother of vinegar. This will be
filtered out. And the vinegar will be bottled and pasteurized at 140160F
for 30mins.

II.

Trickling method
Next is is the rapid generator or trickling method. Trickling method
is done with a wooden chamber filled with wooden shavings which
contains the bacteria acetobacter. There were air supply at the
bottom allowing oxygen into the system. From the top is the
substrate, ethanol which is poured down into the system,
distributed via sprayers. So, as the substrate travel down through
the bacteria containing shavings, the bacteria catalyzes the process
of oxidation and produces aceticc acid. The reason behind the
shavings is to add physical contact between the substrate and the
bacteria. Then the acetic acid reaches the bottom most part of the
fermenter, it is then collected in the exit.

III.

Submerged Method

In the submerged process, the bacteria, acetobacter is added into

the system with water. Here, a blade or a fan is used to agitate the
system is also where the supply of oxygen comes from. The
substrate, ethanol is introduced into the container (by the way, this
process is done by batch. The fermenter is surrounded by heat
jackets to regulate ideal temperature for the process. So when
agitating, the physical contact between the bacteria and the
substrate is hastened and produces acetic acid faster than the
previous processes.
b. Lactic Acid
This reaction is an anaerobic fermentation which means that oxygen
is not present in the production, this because as glycolysis proceeds
it is naturally followed up by Krebs cycle, etc. and only when the
bacteria is deprived with oxygen that it will choose to take the lactic
acid producing path. So, here, glucose undergo glycolysis and is
cleaved into 2 mole pyruvate, and the pyruvate is the converted
into Lactate by Pyruvate dehydrogenase which is excreted by the
Lactobacillus bacteria.

A simple design of a lactic acid producing plant.

Starting with the sugar rich feedstock (e.g. skim milk) which is fed
into the fermentor.

In the fermentor, the occurs the rection of glucose to lactate, which

is then filtered twice to achieve desired purity.

c. Citric Acid
Like the Lactic acid production, the process starts with glycolysis which
breaks down 1 mole of glucose into 2 molesof pyruvate. However, this
process, unlike Lactic acid production, is aerated, e.i. supplied with
oxygen in order to proceed. This gives way to the citric acid cycle
known as the Krebs Cycle:

This is a simple schematic of Citric Acid production from The National

University of Malaysia.
It starts with the fermentation of glucose by Aspergillus Niger in a
submerged fermenter, pumped through multistage of filtration to
produce high grade citric acid. The reaction in the primary submerged
fermenter is transforming Glucose to Citrate which is recovered and
transformed into Citric acid
Discuss how enzymes work in fermentation processes

What are enzymes?

Enzymes are proteins (complex amino acid structures) made by live cells,
although not all proteins are enzymes. Enzymes have many natural sources
including (1) microbial, i.e. yeast or bacteria, (2) plants, and (3) animals. They
bring molecules together in optimal orientations to make and break chemical
bonds. Enzymes are biological catalysts in the form of proteins that catalyze
chemical reactions in the cells of living organisms. [1]
How do they work?

Structure:

Mechanism:
Enzymes are generally globular proteins, acting alone or in larger
complexes. Like all proteins, enzymes are linear chains of amino acids that
fold to produce a three-dimensional structure. Fold or protein folding is the
process by which a protein structure assumes its functional shape or
conformation. Enzymes are usually much larger than their substrates.
Sizes range from just 62 amino acid residues, for the monomer of 4oxalocrotonate tautomerase, to over 2,500 residues in the animal fatty
acid synthase. Only a small portion of their structure (around 24 amino
acids) is directly involved in catalysis: the catalytic site. The sequence of
the amino acids specifies the structure which in turn determines the
catalytic activity of the enzyme.
Enzymes must bind their substrates before they can catalyse any chemical
reaction. Enzymes are usually very specific as to what substrates they
bind and then the chemical reaction catalysed. Specificity is achieved by
binding
pockets
with
complementary
shape,
charge
and
hydrophilic/hydrophobic characteristics to the substrates. Enzymes can
therefore distinguish between very similar substrate molecules to be
chemoselective, regioselective and stereospecific.

To explain the observed specificity of

enzymes, in 1894 Emil Fischer
proposed that both the enzyme and
the
substrate
possess
specific
complementary geometric shapes
that fit exactly into one another. This
is often referred to as "the lock and
key" model. This early model explains
enzyme specificity, but fails to explain
the stabilization of the transition state
that enzymes achieve. Then later on,
in 1958, Daniel Koshland suggested a
modification to the lock and key
model: since enzymes are rather
flexible structures, the active site is
continuously reshaped by interactions with the substrate as the substrate
interacts with the enzyme. As a result, the substrate does not simply bind
to a rigid active site; the amino acid side-chains that make up the active
site are molded into the precise positions that enable the enzyme to
perform its catalytic function. It is called induced fit model. [2]
Enzyme catalysis is the increase in the rate of a chemical reaction by the
active site of a protein. The mechanism of enzyme catalysis is similar in
principle to other types of chemical catalysis. By providing an alternative
reaction route the enzyme reduces the energy required to reach the
highest energy transition state of the reaction. The reduction of activation
energy increases the amount of reactant molecules that achieve a
sufficient level of energy, such that they reach the activation energy and
form the product. As with other catalysts, the enzyme is not consumed
during the reaction (as a substrate is) but is recycled such that a single
enzyme performs many rounds of catalysis. [3]
How do enzymes work in fermentation processes?
Fermentation is the process of anaerobic decomposition of organic substances
(primarily carbohydrates); it occurs under the influence of microorganisms or
the enzymes secreted by them. In the course of fermentation, the energy
needed for the vital activity of the microorganisms is released as a result of
conjugated oxidation-reduction reactions, and chemical compounds used by the
microorganisms for biosynthesis of amino acids, proteins, organic acids, fats,
and other body components are formed.
Many aspects of fermentation require enzymatic reactions in order to proceed.
Extracting fermentable sugars from grains are critical to the success of yeast
fermentation, and production of alcohol could not occur without the work of
amylase enzymes to break down starch into simple sugars that are usable by
yeast. Also, many steps of the metabolic pathways used by yeast are enzymedependent. Without enzymes, fermentation would not be possible.
(A short video will be presented. [4])
Pharmaceutical Industries

The pharmaceutical industry is an important component of health care system throughout the world; it
is comprised of many public and private organizations that discover, develop, manufacture and market
medicines for human and animal health. It is based primarily upon the scientific research and
development of medicines that prevent or treat diseases and disorders. Pharmaceutical manufacturing
is divided into two major stages: (a) the production of the active drugs (primary processing) and (b)
the secondary processing, the conversion of the active drugs into products suitable for administration.
[1]
The main pharmaceutical groups manufactured include:

Proprietary ethical products or prescription only medicines (POM), which are usually
patented products
General ethical products, which are basically standard prescription-only medicines made to a
recognized formula that may be specified in standard industry reference book
Over the counter (OTC), or nonprescription products.

The products are available as tablets, capsules, liquids, creams, ointments and aerosols, which contain
inhalable products or products suitable for external use.
Manufacturing Processes in the Pharmaceutical Industry
Basic production of bulk drug substances may employ three major types of processes: fermentation,
organic chemical synthesis, and biological and natural extraction. These manufacturing operations
may be discrete batch, continuous or a combination of these processes. Antibiotics, steroids, and
vitamins are produced by fermentation, whereas many new drug substances are produced by organic
synthesis. Historically, most drug substances were derived from natural sources such as plants,
animals, fungi and other organisms. Natural medicines are pharmacologically diverse and difficult to
produce commercially due to their complex chemistry and limited potency.
Fermentation
Fermentation is a biochemical process employing selected microorganisms and microbial
technologies to produce a chemical product. Batch fermentation processes involve three basic steps:
inoculum and seed preparation, fermentation, and product recovery or isolation. Inoculum preparation
begins with a spore sample from a microbial strain. The strain is selectively cultured, purified and
grown using a battery of microbial techniques to produce the desired product. The spores of the
microbial strain are activated with water and nutrients in warm conditions. Cells from the culture are
grown through a series of agar plates, test tubes and flasks under controlled environmental conditions
to create a dense suspension.

What is Penicillin?
-an antibiotic or group of antibiotics produced naturally by certain blue molds
and now usually synthetically
- Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming.
1.) Seed culture
Kingdom: Fungi
Family: Trichocomaceae
Genus: Penicillium
Species: P. chrysogenum
The Penicillium chrysogenum is a fungi that is the source of penicillin
The seed culture is developed first in the lab by the addition of Penicillium spores
into a liquid medium

Recommended Media:

Corn Meal Agar

Malt Extract Agar

Potato Agar

Wort Agar

Incubate at 25C for 2-7 days

Culture flasks are used for growing microorganisms; these are shaken generally
by a gyratory shaker at 200-250 r.p.m. The shaker rotates horizontally. This is to
keep the cells and the nutrients in the growth media homogeneous in the growth
media homogeneous and to increases the rate of oxygen uptake by the media.
2.) Preparation of Medium for Penicillium fungus
The medium usually contain its carbon source which is found in corn
steep liquor and glucose. Medium also consist of salts such as Magnesium
sulphate, Potassium phosphate and Sodium nitrates. They provide the essential
ions required for the fungus metabolic activity.
3.) Sterilization
Medium is sterilize at high heat and high pressure usually through a holding tube
or sterilize together with the fermenter. The pressurized steam is use usually and
the medium is heated to 121C at 30psi or twice of atmospheric pressure for 15
mins. High temperature short time conditions are use to minimize
degradation of certain components of the media.
All the fermentation processes are not aseptic so contamination by microbes
need to be maintained minimum thats why it need to be sterilize.
4.) Fermentation
Fermentation for penicillin is usually done in the fed-batch
To avoid:
Glucose Effect excess sugar leads to formation of ethanol and other acids that
inhibits cell growth and metabolic activities
Catabolite Repression high glucose results in increase of the intracellular
concentration of ATP that leads to repression of enzyme
Thus, low yield of penicillin production as excessive glucose inhibit
penicillin production.

The fermentor is operated at a constant growth temperature to achieve required

growth rate.
Since cells liberate heat during growth, a constant temperature is maintained
using either cooling jackets surrounding the fermentor
The temperature needs to be maintained at 20C - 24C and ph of 6.0 - 6.5.
The pressure in the bioreactor is usually much higher than the atmospheric
pressure(1.02atm) this is to prevent contamination from occurring as it
prevents external contaminants from entering.
Sparging of air bubbles is necessary to provide sufficient oxygen, the viability of
the fungus. Depending on the volume of medium, for 2 cubic metres of culture,
the sparging rate should be about 2.5 cubic metres per minute.
The paddle wheel is used to keep the mixture of cells and growth media inside
the fermenters relatively homogenize. It also increases oxygen mass transfer by
decreasing the size of the oxygen bubbles. The impeller is necessary to mix the
culture evenly throughout the culture medium, fungal cells are much hardy and
they are able to handle rotation speed of around 200rpm
5.) Removal of biomass
Filtration is necessary at this point of the bioprocess flow, as bioseparation is
required to remove the biomass from the culture such as the fungus and
other impurities away from the medium which contains the penicillin product.
The Rotary Vacuum filter is commonly employed as it able to run in
continuous mode in any large scale operations.
6.) Adding of solvent
In order to dissolve the penicillin present in the filtrate, organic solvents such as
amyl acetate or butyl acetate are use as they dissolve penicillin much better

than water at physiological pH. At this point, penicillin is present in the solution
and any other solids will be considered as waste.
7.) Centrifugal extraction
Centrifugation is done to separate the solid waste from the liquid component
which contains the penicillin. Usually a tubular bowl or chamber bowl
centrifuge is use at this point. The supernatant will then be transferred further
in the downstream process to continue with extraction.
Tubular Bowl Centrifuge

In tubular-bowl centrifuges, feed enters from the bottom of the cylindrical bowl.
A distributor and baffle assembly accelerates the incoming liquid to rotor speed.
The centrifugal force acts on the solvent entering and separates the liquid
(supernatant) and solids according to their specific gravities. The lighter
substance forms the inside layer and heavier substance forms the outer layer.
The supernatant will then be transferred further in the downstream process to
continue with extraction.
8.) Extraction
Penicillin dissolve in the solvent will now undergo a series of extraction process
to obtain better purity of the penicillin product.
The acetate solution is first mixed with a phosphate buffer, followed by a
chloroform solution, and mixed again with a phosphate buffer and finally in
an ether solution.
Penicillin is present in high concentration in the ether solution and it will be
mixed with a solution of sodium bicarbonate to obtain the penicillin-sodium
salt, which allow penicillin to be stored in a stable powder form at room
temperature.
The penicillin-sodium salt is obtained from the liquid material by basket
centrifugation, in which solids are easily removed.
Basket Centrifugation

As the basket rotates, a slurry solution is fed into the centrifuge via an inlet pipe.
The centrifugal force pushes the slurry against the rotating basket, forcing the
liquid to pass through the perforations, and the solids or filter cake to remain
behind, accumulating on the sides of the basket.
9.) Fluid bed drying
Drying is necessary to remove any remaining moisture present in the powdered
penicillin salt. In fluid bed drying, hot gas is pump in from the base of the
chamber containing the powdered salt inside a vacuum chamber. Moisture is
then remove in this manner and this result in a much drier form of penicillin.
In the fluidized bed dryer, hot air or gas is passed at high pressure through a
perforated bottom of the container containing granules to be dried. The granules
are suspended in the stream of air and are lifted from the bottom. This condition
is called fluidized state. The hot air is surrounded every granules to completely
dry them. Thus materials or granules are uniformly dried.
Organic Chemical Synthesis
Chemical synthesis processes use organic and inorganic chemicals in batch
operations to produce drug substances with unique physical and pharmacological
properties. Typically, a series of chemical reactions are performed in multipurpose reactors and the products are isolated by extraction, crystallization and
filtration (Kroschwitz 1992)

Reactors

The most common type of reactor vessel is the kettle-type reactor. These
reactors typically range in capacity from 50 to several thousand gallons. The
vessels are made of either stainless steel or glass-lined carbon steel.
The reactor can be operated at atmospheric pressure, elevated pressure, or
under vacuum. Because of their flexibility, reactors may be used in a variety of

ways. Besides hosting chemical reactions, they can act as mixers, heaters,
holding tanks, crystallizers, and evaporators. (USEPA, 1979)
Biological and Natural Extraction
Natural product extraction, as the name suggests, involves isolating an active
ingredient from natural sources, such as plants, roots, parasitic fungi or animal
glands. This process is often used to produce allergy relief medicines, insulin,
morphine, anti-cancer drugs, or other pharmaceuticals with unique properties

The desired active ingredient, usually present in raw materials at very low
concentrations, must be extracted for the final product.
Therefore, a defining characteristic of this process is that the volume of
finished product is often an order of magnitude smaller than that of the
raw materials used
Biological and Natural Extraction is EXPENSIVE
For more economical process: as the volume of material being processed
decreases, the size of the containers carrying the material also decreases.
Pharmaceutical Manufacturing of Dosage form Products
The primary objective of mixing, compounding, or formulating operations are to
convert the manufactured bulk substances into a final, usable form. (USEPA
1995)
Formulation and packaging is performed in accordance with good
manufacturing practices (GMP). GMP is regulated by the FDA and sets forth
the minimum methods to be used in, and the facilities and controls to be used for
the manufacture, processing, packing, or holding of a drug to assure that such

drug meets the safety requirements and the quality and purity characteristics
that it purports or is represented to possess

How Tablets are made?

ingredients: API
Filler: Sugar or Starch
Binder: Corn Syrup
Lubricant: Magnesium sterate
Process: Wet Granulation
1.)the active ingredient is powdered and mixed with the filler This mixture is then
wetted and blended with the binder, forming a solution.
2.)Coarse granules form which are mixed with lubricants such as magnesium
stearate and then compressed into tablets
3.) These large tablets are then ground and screened to a desired mesh size
then recompressed into final tablets
Coating may be used to offer protection from moisture, oxygen, or light, to
mask unpleasant taste or appearance, and to impart distinctive colors to
facilitate patient recognition.
Enteric coatings are used to delay the release of the active ingredient in the
stomach and prolong therapeutic activity.

Ever wonder about the squishy shell of a capsule?

Capsules Shells are formed by dipping metal pins into a solution of gelatin of a
specific temperature. The temperature controls the viscosity of the gelatin
and hence the thickness of the capsule walls. When the pins are removed
from the solution, a hard coating of gelatin forms on the pins. The coating is
dried and trimmed.
These capsules are filled by introducing the powdered material into the longer
end or body and the capsule and then slipping on the cap. (Remington, 1995)

References
(Introduction)
[1] .Current developments in Fermentation (n.d.). Chem. Eng.
81(26)98(1974);ECT,3d ed.,vol.9,1980,pp.861-880. Retrieved November 19,
2015
[2] Wailen, Stodola and Jackson (1959). Type Reactions in Fermentation
Chemistry. Retrieved November 19, 2015, from http://Dept.ofAgri.,/Agricultural
research.htm
[3] Silcox and Lee (n.d.). Fermentation, ind eng. Chem.40 1602, 1948. Retrieved
November 19, 2015
(Alcohol, Acids and Acetone)
[1] Shreeve (n.d.). Chemical Industry Processes. Retrieved November 19, 2015
[2] Ethanol Fermentation (n.d.). Retrieved November 19, 2015, from
https://en.wikipedia.org/wiki/Acetone%E2%80%93butanol
%E2%80%93ethanol_fermentation
[3] Acetone. (n.d.). Retrieved November 19, 2015, from
http://www.icis.com/resources/news/2007/11/01/9074860/acetone-productionand-manufacturing-process/
[4] Alcohols. (n.d.). Retrieved November 19, 2015, from
http://www.gitam.edu/eresource/environmental/em_maruthi/industrial.htm
[5] Acids. (n.d.). Retrieved November 19, 2015, from
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