Industrial

manufacture and
testing of aspirin
By Irini, Ella, Nella, and Adelaide
How is aspirin
made in
industry?
•

• Aspirin is synthesized industrially through a process

called esterification.
• In industry, aspirin is made in a batch process. It is made
in a much higher quantity than you would make in a
laboratory.
• The following slides outline the industrial process of how
aspirin is made:
•
 WATER

Ethanoic REACTOR
acid

Toluene

Hydroxybenzoic
acid
WATER
88-92dc
20
hours
SOLIDS

FILTER WASHER

Cooling filtrate WASH

tanks acetyl
salicylic acid Filter to
(aspirin) PACKAGING recover DRIER
Purify, test, make
tablets
 How is aspirin synthesized?

• Salicylic acid production

• The starting material for aspirin synthesis is salicylic

acid, which can be obtained from various sources,
including naturally from the bark of the willow tree
or through synthetic processes.
• There are several methods to produce salicylic acid,
but one common method is through the reaction of
phenol with sodium hydroxide and carbon dioxide,
followed by acidification. This produces sodium
salicylate, which is then acidified to yield salicylic
acid.
Acetylation reaction
• Acetylation Reaction: In the
industrial synthesis of aspirin,
salicylic acid is reacted with
acetic anhydride in the presence
of a catalyst, typically sulfuric
acid. This reaction is known as
esterification. The acetyl group
(-COCH3) from acetic anhydride
replaces the hydrogen atom in
the hydroxyl (-OH) group of
salicylic acid, resulting in the
formation of acetylsalicylic acid
(aspirin) and acetic acid as a
byproduct.
•
The reactor
• - glass lined
• Stainless steel
• Heated by steam
•
Purification
• After the reaction, the mixture is typically cooled,
and the aspirin product precipitates out of solution.
The crude aspirin is then filtered and washed to
remove impurities and any remaining acetic acid.
• Purification is necessary to obtain pure aspirin. The
common method used is recrystallization, and
this will be explained on the following slide.
Filter press – purification
• A filter press is a type of equipment
used in various industries, including
pharmaceuticals, chemicals, food
and beverage, mining, and
wastewater treatment. It's designed
for separating solids from liquids
through pressure filtration.
• The filter press produces very dry
products. The press consists of a
series of filter plates which are held
together during the process. During
filtration, slurry can flow in, and
filtrates can flow out. The slurry is
pumped into the middle of the plates
where it then spreads between
them. Filter cake builds up on the
filter cloth and this in turn acts like a
filter.
recrystallization
• The purified aspirin is often recrystallized from a
suitable solvent to further purify it and obtain
aspirin crystals of higher quality.
• 1) The crude aspirin is dissolved in a suitable
solvent, often hot ethanol or water. This creates a
solution where aspirin and impurities are dissolved.
• 2) The solution is allowed to cool slowly. As it cools,
pure aspirin crystals start to form while impurities
remain dissolved.
• 3) The mixture is then filtered to separate the solid
aspirin crystals from the impurities in the solution.
Drying and packaging
• The collected aspirin crystals are washed with a
small amount of cold solvent to remove any
remaining impurities. Then, the crystals are dried
to remove the solvent, leaving behind pure aspirin.
• Finally, the dried aspirin is milled into a fine powder
and packaged for distribution and sale.
drying techniques in
industry – spray
drying
• In industry, large amounts of wet
solid needs to be dried. A method
known as spray drying is
commonly used. Spray drying
involves using hot gas to produce
a dry powder.
• A spray nozzle or atomiser is used
to spray the slurry into the hot
gas. The air is often blown in at
the same time as the liquid. The
hot drying gas can flow with or
against the slurry solid.
Freeze drying
• Freeze drying is a pharmaceutical
process that removes water from
sensitive drugs or biological
products by freezing them and
then evaporating the frozen water
in a vacuum, leaving behind a dry
and stable product, which gives
the product a longer shelf life.
Stages of freeze drying
• 1) Pre-treatment. This occurs before the freeze drying and may
involve concentrating the product and/or adding
preservatives.
• 2) Freezing. This process is usually done in a freeze-drying
machine. Firstly, the material is cooled below the lowest
temperature at which the solid and liquid phases of the
material can co-exist. This ensures that sublimation (where a
solid becomes gas without becoming a liquid first) rather than
melting will occur. Usually, freezing temperatures are
between -50- and -80-degrees C. The freezing phase is very
important because if not done properly, the whole product
could be spoiled.
3) Primary drying. The pressure is lowered, and enough heat is
supplied to the material for the ice to sublime. Around 95% of
the water is sublimated. This phase can take several days in
industry because if too much heat is added, the materials
structure could be altered. In this phase some proteins denature
with high temperatures. Pressure is controlled using a partial
vacuum which speeds up the sublimation. Vapour is produced
more quickly in order to fill the partial vacuum.
4) Secondary drying. In this stage, unfrozen water molecules are
removed. The temperatures are raised higher than in the
primary drying phase to break any interactions that have formed
between the water molecules and the frozen material. After the
freeze-drying process is complete, the vacuum is usually broken
with an inert gas such as nitrogen, before the material is sealed.
Comparison of laboratory and industrial
manufacture and testing of aspirin
Aspirin is a widely used medication that can be
produced in laboratory and industrial settings. Whilst
the principles of aspirin production are the same in
both settings, there are differences in the equipment,
technique testing, raw materials, and scale of
production.
Equipment - SIMILARITIES
• Heating and Cooling Equipment- Both settings may use heating
mantles, hot plates, and water baths for controlling reaction
temperatures. Furthermore, cooling equipment like condensers may
also be employed to control exothermic reactions and maintain
desired temperatures.
• Filtration Equipment- Filtration is often a crucial step in both
laboratory synthesis and industrial manufacture. Both settings may
use vacuum filtration systems, filter paper, and filtration
apparatuses to separate solid products from reaction mixtures.
• Analytical Instruments- Both setting may use analytical instruments
such as spectrophotometers, chromatography systems, and titration
setups for quality control and analysis of reaction products.
•

•
Equipment - DIFFERENCES
•

• Laboratories typically use small-scale glassware and basic laboratory

equipment like beakers, flasks, and hot plates, while industrial
manufacturing requires equipment such as reactors, pumps,
distillation columns, and filtration systems designed for large-scale
production.
• Specialized Equipment- Industrial facilities may use specialized
equipment tailored to the specific requirements of aspirin
production, such as large- scale filtration and drying equipment.
•
Techniques - SIMILARITIES
• Synthesis Process- Both in the laboratory and in industrial settings, aspirin is synthesized
using the same basic chemical reaction, which involves the acetylation of salicylic acid
using acetic anhydride or acetyl chloride.
• Reaction Conditions- The reaction conditions such as temperature, pressure, and catalysts
used in laboratory synthesis are often scaled up and optimized for industrial production,
but the underlying principles remain the same.
• Purification Techniques: After synthesis, purification techniques such as recrystallization are
employed both in the laboratory and industrial settings to isolate the aspirin production
from impurities.
• Safety Protocols- Both environments adhere to strict safety protocols to ensure the well-
being of personnel and the integrity of the product. This includes the use of personal
protective equipment (PPE), proper ventilation systems, and adherence to chemical
handling procedures.
• Quality Control- Quality control measures are implemented in both settings to monitor the
consistency and purity of the aspirin product. This includes regular testing of raw material,
intermediates, and final products to ensure compliance with regulatory standards.
• Equipment and Apparatus- While the scale and complexity of equipment may vary between
laboratory and industrial settings, similar types of equipment such as reaction vessels,
stirring apparatus, and analytical instruments are utilized in both environments.
•
Techniques- DIFFERENCES
•

Although the principle remains the same, safety protocols may be

slightly different due to the differences in scale of production and
equipment used. In a laboratory setting you would be equipped with lab
coats, safety goggles and gloves. The same applies to an industrial
environment, except there are more protocols such as using ventilation
systems because there is a higher risk of injury/illness.
The size/scale of the equipment varies due to differences in the amount
of aspirin that is produced – bigger reaction vessels are used in industry
compared to in a lab.
Testing – SIMILARITIES
• Quality Control- Both environments require rigorous quality control measures to
ensure that the aspirin produced meets safety, efficacy, and regulatory
standards.
• Standard Operating Procedures (SOPs)- Both settings utilize standardized
operating procedures to conduct texts consistently and accurately. These
SOPs ensure that the testing process is reliable and reproducible.
• Calibration and Maintenance of Equipment- Regular calibration and
maintenance of testing equipment are necessary in both settings to ensure
the accuracy and reliability of test results.
• Validation of Test Methods- Test methods that are used for analysing aspirin
samples (such as chromatography) must be validated to demonstrate their
accuracy, precision, and specificity. This validation process is essential in both
college laboratories and industrial settings to ensure the reliability of test
results.
• Safety- Safety protocols and procedures are essential in both environments to
protect personnel and ensure compliance with regulations.
Testing – DIFFERENCES
• Time Constraints- Industrial manufacturing processes are often
optimized for efficiency and speed, while college laboratory
experiments may prioritise thoroughness and learning over speed.
•
Raw materials – SIMILARITIES
• Acetylsalicylic Acid- This is the primary active ingredient in aspirin,
and it’s the same compound used both in laboratory and industrial
production. It is usually synthesized from salicylic acid and acetic
anhydride in both se8ttings.
• Salicylic Acid- Often used as the starting material for the synthesis of
Acetylsalicylic Acid, salicylic acid is a common raw material in both
laboratory and industrial contexts.
• Acetic Anhydride- Another key reagent in the synthesis of aspirin,
acetic anhydride is used to acetylate salicylic acid to produce
aspirin. It’s utilized both in laboratory and industrial processes.
• Sulfuric Acid (catalyst)- Often used as a catalyst in the synthesis
process, sulfuric acid helps facilitate the reaction between salicylic
acid and acetic anhydride to form aspirin. It’s employed in both
laboratory and industrial- scale synthesis. .
•
Raw materials – DIFFERENCES
• Purity- Raw materials used in industrial settings often require higher
purity levels compared to those used in laboratory settings.
Industrial processes typically demand consistent quality and purity
to meet regulatory standards and ensure the reproducibility of the
final product.
• Scale- Laboratory syntheses are typically conducted on a much
smaller scale compared to industrial production. Industrial processes
are optimized for large- scale production, which may necessitate/
require equipment and handling procedures for raw material
Scale of production –
• Laboratory production typically occurs on a small scale, often in
quantities measured in grams or milligrams, while industrial
manufacturing involves much larger-scale production, often
measured in tons or kilograms.
Waste management