The document summarizes the key steps involved in manufacturing oral solid dosage forms like tablets. It involves size reduction of raw materials, blending, granulation, drying, lubrication, compression into tablets, coating if needed, and final packaging. Precise control of critical process parameters is required at each stage to ensure quality, bioavailability and stability of the final tablets. Granulation is an important step for uniform distribution of drugs in the blend and influences tableting process. Drying is also critical to control residual moisture. Compression forms the tablets and critical parameters like hardness and disintegration time need to be monitored.

1. AUTHOR - ASAD K. MULLA.
B.Pharmacy

2. The manufacture of oral solid dosage forms such as
tablets is a complex multi-stage process under which the
starting materials change their physical characteristics a
number of times before the final dosage form is
produced. Traditionally, tablets have been made by
granulation, a process that imparts two primary requisites
to formulate: compactibility and fluidity. Both wet
granulation and dry granulation (slugging and roll
compaction) are used. Regardless of whether tablets are
made by direct compression or granulation, the first step,
milling and mixing, is the same; subsequent steps differ.
Numerous unit processes are involved in making tablets,
including particle size reduction and sizing, blending,
granulation, drying, compaction, and (frequently) coating.
Various factors associated with these processes can
seriously affect content uniformity, bioavailability, or
stability.

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5. The sifting and sizing (size reduction, milling, crushing, grinding,
pulverization) is an important step in the process of tablet
manufacturing.
In manufacturing of compressed tablets, the mixing or blending of
several solid pharmaceutical ingredients is easier and more uniform
if the ingredients are about the same size. This provides a greater
uniformity of dose. A fine particle size is essential in case of lubricant
mixing with granules for its proper function.
Advantages of smaller tablets are as follows:
Increased surface area, which may enhance an active ingredient's
dissolution rate and hence bioavailability
Improved tablet-to-tablet content uniformity due to a larger number
of particles per unit weight
Controlled particle size distribution of dry granulation or mix to
promote better flow of mixture in tablet machine
Improved flow properties of raw materials
Improved colour and/or active ingredient dispersion in tablet
excipients
Uniformly sized wet granulation to promote uniform drying

6. Following particle size reduction and blending, the
formulation may be granulated, which provides
homogeneity of drug distribution in blend. This process
also is very important and needs experience to attain
proper quality of granule before tableting, quality of
granule determines the smooth and trouble free process of
tablets manufacturing.Please keep in mind, if one can not
have experience of granulation, can make great troubles for
tableting press operator.
Process Critical Parameters During Process:-
Dry mixing
Impeller speed
Chopper
Mixing time
Granulation
Kneading during Binder addition
Kneading at slow Speed after Binder addition
Kneading at slow speed

7. Drying is a most important step in the formulation and
development of pharmaceutical product. It is important
to keep the residual moisture low enough to prevent
product deterioration and ensure free flowing properties.
The commonly used dryers include Fluidized – bed dryer,
Vacuum tray dryer, Microwave dryer, Spray dryer, Freeze
dryer, Turbo - tray dryer, Pan dryer, etc.
Process Critical Parameters During Process:-
Drying
Inlet Temperature
Outlet temperature
Product bed temperature
Dutch sieve Integrity before and after use

8. The successful mixing of powder is more difficult than mixing
liquid, as perfect homogeneity is difficult to achieve. A further
problem is the inherent cohesiveness and resistance to
movement between the individual particles. The process is
further complicated in many systems by the presence of
substantial segregation influencing the powder mix. This arises
from the difference in size, shape, and density of the
component particles. The powder/granules blending are
involved at stage of pre granulation and/or post granulation
stage of tablet manufacturing. Each process of mixing has an
optimum mixing time, and longer mixing may result in an
undesired product. The optimum mixing time and mixing
speed must be evaluated. Blending prior to compression is
normally achieved in a simple tumble blender. The blender
may be a fixed blender into which the powders are charged,
blended and discharged. It is now common to use a bin
blender.

9. Process Critical Parameters During Process:-
Lubrication
Lubrication Time
RPM of cage blender
Yield of lubricated granules

10. After the preparation of granules (in case of wet
granulation) or sized slugs (in case of dry granulation) or
mixing of ingredients (in case of direct compression), they
are compressed to get final product. The compression is
done either by single punch machine (stamping press) or by
multi station machine (rotary press). The tablet press is a
high-speed mechanical device. It 'squeezes' the ingredients
into the required tablet shape with extreme precision. It
can make the tablet in many shapes, although they are
usually round or oval. Also, it can press the name of the
manufacturer or the product into the top of the tablet. .
Each tablet is made by pressing the granules inside a die,
made up of hardened steel. The die is a disc shape with a
hole cut through its centre. The powder is compressed in
the centre of the die by two hardened steel punches that fit
into the top and bottom of the die.The punches and dies
are fixed to a turret that spins round. As it spins, the
punches are driven together by two fixed cams - an upper
cam and lower cam. . The top of the upper punch (the
punch head) sits on the upper cam edge .The bottom of the
lower punch sits on the lower cam edge.

11. Stage 1: Top punch is withdrawn from the die by the upper
cam Bottom punch is low in the die so powder falls in
through the hole and fills the die
Stage 2: Bottom punch moves up to adjust the powder
weight-it raises and expels some powder.
on the tablets; punches with recessed etchings produce
tablets with raised impressions or monograms. Logos may
be placed on one or on both sides of a tablet, depending on
the punches.
The shapes of the two cams determine the sequence of
movements of the two punches. This sequence is repeated
over and over because the turret is spinning round. The force
exerted on the ingredients in the dies is very carefully
controlled. This ensures that each tablet is perfectly formed.
Because of the high speeds, they need very sophisticated
lubrication systems. The lubricating oil is recycled and
filtered to ensure a continuous supply. Common stages
occurring during compression

12. Process Critical Parameters During Process:-
Compression
Granules flow from granule's
container to Feeder
Machine Overload pressure
Appearance
Weight of 20 tablets
Individual weight variation
Hardness
Tablet thickness
Friability
Disintegration Time
Yield
Coating
Baffle type
Spray Nozzle Aperture
Pan Load
Temperature of Inlet air
Temperature of Exhaust air
Coating Pan RPM
Atomizing Pressure
Spray Rate
Distance Between gun &
tablet bed
Average Weight gain
Yield

13. Tablets must be packaged before they can be sent out for
distribution. The type of packaging will depend on the
formulation of the medicine.
Blister packs are a common form of packaging. They are safe
and easy to use and the user can see the contents without
opening the pack. Many pharmaceutical companies use a
standard size of blister pack. This saves the cost of different
tools and changing the production machinery between
products. Sometimes the pack may be perforated so that
individual tablets can be detached. This means that the
expiry date and the drug's name must be printed on each
part of the package. The blister pack itself must remain
absolutely flat as it travels through the packaging processes,
especially when it is inserted into a carton. Extra ribs are
added to the blister pack to improve its stiffness.
Process Critical Parameters During Process:-
Packing
Sealing Roller Temperature
Leak Test
Yield