The Manufacturing

Process
Aspirin tablets are manufactured in different shapes. Their weight,
size, thickness, and hardness may vary depending on the amount of
the dosage. The upper and lower surfaces of the tablets may be flat,
round, concave, or convex to various degrees. The tablets may also
have a line scored down the middle of the outer surface, so the tablets
can be broken in half, if desired. The tablets may be engraved with a
symbol or letters to identify the manufacturer.
Aspirin tablets of the same dosage amount are manufactured in
batches. After careful weighing, the necessary ingredients are mixed
and compressed into units of granular mixture called slugs. The slugs
are then filtered to remove air and lumps, and are compressed again
(or punched) into numerous individual tablets. (The number of tablets
will depend on the size of the batch, the dosage amount, and the type
of tablet machine used.) Documentation on each batch is kept
throughout the manufacturing process, and finished tablets undergo
several tests before they are bottled and packaged for distribution.
The procedure for manufacturing hard aspirin tablets, known as dry-
granulation or slugging, is as follows:

Weighing
1 The corn starch, the active ingredient, and the lubricant are
weighed separately in sterile canisters to determine if the
ingredients meet pre-determined specifications for the batch size
and dosage amount.

Mixing
2 The corn starch is dispensed into cold purified water, then
heated and stirred until a translucent paste forms. The corn
starch, the active ingredient, and part of the lubricant are next
poured into one sterile canister, and the canister is wheeled to a
mixing machine called a Glen Mixer. Mixing blends the
ingredients as well as expels air from the mixture.
 3 The mixture is then mechanically separated into units, which
are generally from 7/8 to 1 inches (2.22 to 2.54 centimeters) in
size. These units are calledslugs.

Dry screening
4 Next, small batches of slugs are forced through a mesh screen
by a hand-held stainless steel spatula. Large batches in sizable
manufacturing outlets are filtered through a machine called a
Fitzpatrick mill. The remaining lubricant is added to the mixture,
which is blended gently in a rotary granulator and sifter. The
lubricant keeps the mixture from sticking to the tablet machine
during the compression process.

Compression
5 The mixture is compressed into tablets either by a single-punch
machine (for small batches) or a rotary tablet machine (for large
scale production). The majority of single-punch machines are
power-driven, but hand-operated models are still available. On
single-punch machines, the mixture is fed into one tablet mold
(called a dye cavity) by a feed shoe, as follows:

o The feed shoe passes over the dye cavity and releases the
mixture. The feed shoe then retracts and scrapes all excess
mixture away from the dye cavity.

o A puncha short steel rodthe size of the dye cavity

descends into the dye, compressing the mixture into a
tablet. The punch then retracts, while a punch below
 This drawing illustrates the principle of compression in a single-punch
machine. First, the aspirin mixture is fed into a dye cavity. Then, a steel
punch descends into the cavity and compresses the mixture into a
tablet. As the punch retracts, another punch below the cavity rises to
eject the tablet.

the dye cavity rises into the cavity and ejects the tablet.

o As the feed shoe returns to fill the dye cavity again, it

pushes the compressed tablet from the dye platform.

On rotary tablet machines, the mixture runs through a feed line

into a number of dye cavities which are situated on a large steel
plate. The plate revolves as the mixture is dispensed through the
feed line, rapidly filling each dye cavity. Punches, both above and
below the dye cavities, rotate in sequence with the rotation of
the dye cavities. Rollers on top of the upper punches press the
punches down onto the dye cavities, compressing the mixture
into tablets, while roller-activated punches beneath the dye
cavities lift up and eject the tablets from the dye platform.

Testing
 6 The compressed tablets are subjected to a tablet hardness and
friability test, as well as a tablet disintegration test (see Quality
Control section below).

Bottling and packaging

7 The tablets are transferred to an automated bottling assembly
line where they are dispensed into clear or color-coated
polyethylene or polypropylene plastic bottles or glass bottles.
The bottles are topped with cotton packing, sealed with a sheer
aluminum top, and then sealed with a plastic and rubber child-
proof lid. A sheer, round plastic band is then affixed to the
circular edge of the lid. It serves as an additional seal to
discourage and detect product tampering.

8 The bottles are then labeled with product information and an

expiration date is affixed. Depending on the manufacturer, the
bottles are then packaged in individual cardboard boxes. The
packages or bottles are then boxed in larger cardboard boxes in
preparation for distribution to distributors.

Finished aspirin tablets often have a line "scored" down the center so that the tablet can
be broken into two parts with ease.

Quality Control
Maintaining a high degree of quality control is extremely important in
the pharmaceutical manufacturing industry, as well as required by the
Food and Drug Administration (FDA). All machinery is sterilized before
beginning the production process to ensure that the product is not
contaminated or diluted in any way. In addition, operators assist in
maintaining an accurate and even dosage amount throughout the
production process by performing periodic checks, keeping meticulous
batch records, and administering necessary tests. Tablet thickness
and weight are also controlled.
Once the tablets have been produced, they undergo several quality
tests, such as tablet hardness and friability tests. To ensure that the
tablets won't chip or break under normal conditions, they are tested
for hardness in a machine such as the Schleuniger (or Heberlein)
Tablet Hardness Tester. They are also tested for friability, which is the
ability of the tablet to withstand the rigors of packaging and shipping.
A machine called a Roche Friabilator is used to perform this test.
During the test, tablets are tumbled and exposed to repeated shocks.
Another test is the tablet disintegration test. To ensure that the tablets
will dissolve at the desirable rate, a sample from the batch is placed in
a tablet disintegration tester such as the Vanderkamp Tester. This
apparatus consists of six plastic tubes open at the top and bottom.
The bottoms of the tubes are covered with a mesh screen. The tubes
are filled with tablets and immersed in water at 37 degrees Fahrenheit
(2.77 degrees Celsius) and retracted for a specified length of time and
speed to determine if the tablets dissolve as designed.