Compression

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Introduction:
• The tablet is currently the most widely used dosage form for oral drug delivery .
• The advantages of the tablet include economy of manufacture, patient convenience, and
compliance.
• Tablets may also offer additional advantages over other dosage forms, such as superior
physical or chemical stability.
• Powder compression is a critical process in manufacturing the tablet dosage form.
• Although this process has been used routinely for over a century, problems related to
powder compression in pharmaceutical formulation development and manufacturing persist,
common problems include tablet failures, such as capping and lamination, powder sticking
to punch surfaces or the die wall, and insufficient mechanical strength to withstand stress in
downstream processing. 2
• The properties of compressed tablets are sensitive to both material characteristics and
process parameters.
• The characteristics of the equipment used and the ambient conditions of temperature and
humidity can also influence tablet compression.
• Physical properties such as particle size, particle shape, crystallinity, and moisture
content influence powder tableting performance by affecting the bonding strength and/or
the bonding area.
• Tablets contain active/s and other excipients selected to aid in the efficiency and safety
in the dosage form

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Tablets:
• A tablet: is a pharmaceutical dosage form , comprises a mixture of active substances
and excipients, usually in powder form, pressed or compacted into a solid.
• The excipients: can include binders, glidants (flow aids) and lubricants to ensure
efficient tabletting; disintegrants to promote tablet break-up in the digestive tract;
sweeteners or flavours to enhance taste; and pigments to make the tablets visually
attractive.
• A polymer coating: is often applied to make the tablet smoother and easier to
swallow, to control the release rate of the active ingredient, to make it more resistant to
the environment (extending its shelf life), or to enhance the tablet's appearance.

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According to drug release rate from the tablet (USP classification):
a- Immediate-release tablet: The tablet is intended to be released rapidly after administration, or the
tablet is dissolved and administered as solution. It is the most common type and includes
1- Disintegrating tablet (conventional or plain tablet)
2- Chewable tablets
3- Effervescent tablets
4- Sublingual and Buccal tablets
5- Lozenges
6- Soluble tablets
b- Modified-release tablet:
• They have release features based on; time, course or location.
• They should be normally swallowed intact.
• Different excipients than immediate release tablets.
• The drug is released from an extended-release tablet slowly at a nearly constant rate
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Tableting Method:

1. Direct compression

2. Granulation

- Dry Granulation

- Wet Granulation

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Tablet Excipients:
1. Fillers (Diluents): are used to increase the bulk of the tablet. It is
generally not feasible to make tablets with a weight of less than about 50 mg.
It is essential that fillers be inert and stable. The range of tablet fillers may
vary from 5-80%. Fillers are also synonymously known as Diluents. Diluents
are used to:
✓ To improve cohesion

✓ To allow direct compression manufacturing

✓ To enhance flow

✓ To adjust weight of tablet as per die capacity 10

Classification of Diluents Based On Their Solubility:
I. Soluble fillers: lactose, sucrose, mannitol, sorbitol.
II. Insoluble fillers: calcium sulfate, dicalcium phosphate, tricalcium phosphate, starch,
calcium carbonate
Selection of the appropriate diluent should be done after considering properties of
diluent such as:
• Compatibility
• Flowability
• Solubility
• Disintegration properties
• hygroscopicity
• Lubricity
• Stability 11
2. Binders:
• are one of an important excipient to be added in tablet formulation.
• In simpler words, binders or adhesives are the substances that promote cohesiveness.
• It is utilized for converting powder into granules through a process known as
granulation. They are either sugars, natural or polymeric materials.
• The type and the percentage of the binder in the formula depend on the API, the other
excipients and the characteristics of the final product.
Added as :
a) powder in direct compression
b) powder then liquid in wet granulation
c) solution in wet granulation
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 Table 11: Classification of Binders

Sugar Natural Binders Synthetic/Semisynthetic Polymer

Sucrose Acacia Methyl Cellulose

Liquid glucose Tragacanth Ethyl Cellulose

Gelatin Hydroxy Propyl Methyl Cellulose ( HPMC)

Starch Paste Hydroxy Propyl Cellulose

Pregelatinized Starch Sodium Carboxy Methyl Cellulose

Alginic Acid Polyvinyl Pyrrolidone (PVP)

Cellulose Polyethylene Glycol (PEG)

Polyvinyl Alcohols

Polymethacrylates

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3. Lubricants:
• Lubricants work by reducing friction by interposing an intermediate layer between the
tablet constituents and the die and / or the punches wall during compression and
ejection and also between particles during compression.
• Since primarily lubricants are required to act at the material interface, lubricants
should be incorporated in the final mixing step, after granulation is complete.
• When hydrophobic lubricants are added to a granulation, they form a coat around the
individual particles (granules), which may cause an increase in the disintegration
time and a decrease in the drug dissolution rate. why?
• (Presence of lubricants may result in a less cohesive and mechanically weaker tablet
because it may interfere with the particle – particle bonding (Lessen tensile strength)).

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• Classification of Lubricants
Lubricants are classified (based on their water solubility) into two groups:
1. Water insoluble
2. Water-soluble
• Water insoluble lubricants are most effective and used at lower concentration than water
soluble lubricants.
• Added with glidant at last step just before compression.

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 Table 12: Water insoluble Lubricants

Insoluble Lubricants Concentration Comments

Stearates (Magnesium Stearate, Calcium Stearate,

0.25-1 Reduce tablet strength and prolong disintegration
Sodium stearate)

Talc 1-2 Insoluble but not hydrophobic, moderately effective.

Sterotex 0.25-1 -

Waxes 1-5 -

Stearowet 1-5 -

Glyceryl behenate (Compritol 888) 1-5 Both lubricant and binder

Liquid paraffin Up to 5 Dispersion problem, inferior to stearates

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Stearic acid and its calcium and magnesium salts are very effective lubricants.
Magnesium stearate is very popular as a lubricant and is preferred to calcium stearate.
Both of these compounds are basics, thus should not be used with acidic drugs.
Water Soluble Lubricants:
• Water Soluble Lubricants are used when a tablet is completely soluble or when
unique disintegration and dissolution characteristics are required.
• Tablet containing soluble lubricant shows higher dissolution rate than tablet with
insoluble lubricants.
• Physical mixture of this lubricant are sodium lauryl sulfate or magnesium lauryl
sulfate with stearates can lead to the best compromise in terms of lubricity, tablet
strength and disintegration.
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 Table 13: Water soluble Lubricants

Water Soluble Lubricants Concentration range (%w/w)

Boric acid 1

Sodium benzoate 5

Sodium oleate 5

Sodium acetate 5

Sodium lauryl sulfate (SLS) 1-5

Magnesium lauryl sulfate (MLS) 1-2

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4. Glidants:
• are added to the formulation to improve the flow properties of the material, which is to be
fed into the die cavity and aid in particle rearrangement within the die during the early
stages of compression.
• If the flow properties are extremely poor then glidants are ineffective and consideration of
force free mechanisms may be necessary.
• The effect of glidants on the flow of the granules depends on the shape and size of the
particle of the glidant and the granule.
• Act by decrease interparticulate friction so improve the flowability
• The commonly used glidants are Talcum, Starch, Colloidal silica silicates,
stearates ( Mg. stearate), calcium phosphate
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5 . Disintegrants:
• are excipients which are added to the tablet or capsule blend to aid in the breakup of
the compacted mass when it is put into a fluid environment.
• This is especially important for immediate release products where rapid release of drug
substance is required.
• Disintegrants can be used with products that are wet granulated, dry granulated and
direct compressed.
• In wet granulation formulations, the disintegrant is normally effective when incorporated
into the granule (intragranularly).
• It may be more effective if added 50% intra-granularly, and 50% extra-granularly.

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Some of the commonly used disintegrant
1. Croscarmellose Sodium (Explotab, Primogel) : High swelling capacity with minimal
gelling, effective at low concentrations ( 2.0% - 6.0%).

2. Crospovidone (Polyplasdone XL, Kollidon CL): water insoluble and strongly hydrophilic.
Rapidly disperses and swells in water, but does not gel even after prolonged exposure.
Greatest rate of swelling compared to other disintegrants.

3. Modified Cellulose- Internally cross-linked form of Sodium carboxymethyl cellulose.

(Accelerates Dissolution),Nymcel. Wicking due to fibrous structure, swelling with minimal
gelling. Effective Concentrations: 1-3% (Direct Compression), 2-4% (Wet Granulation)

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 Single-punch Tablet Machines
• Tableting machines are commonly used in pharmaceutical industry.

• They are high-speed machines that create thousands of tablets in a small period.

• The compounding pharmacist uses a variation of these machines.

• It is called a single-punch tablet press and makes one tablet at a time.

• A "punch" has two pieces of castled tubular metal.

• The bottom metal piece has a small cavity in one end of the tube; the top metal piece has

one end that is tapered into a small rod that will just fit into the small cavity in the other

piece. The rod does not go all the way to the bottom of the cavity, but leaves a small gap.
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• The punch is fitted into a press so that when the handle is depressed and released, the rod
goes into and then comes out of the bottom piece.
• To make a tablet, the powder material is placed into the bottom piece, and the handle is
depressed and released.
• The powders are compressed and occupy the size of the gap designed in the punch.

• Punches come in many sizes which allows the production of tablets of different sizes
and compression strengths.
• But each punch is a matched set; it is not possible to interchange the top and bottom
pieces of different punches.

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Tablet press Consist of:
1. Hopper for storing materials to be pressed
2. Feed frame for distributing materials into dies
3. Dies control size and shape of tablet
4. Punches for compacting the formulation
-lower punch determine the weight of tablet
-upper punch determine the hardness of tablet
5. Cams act as tracks for guiding the moving of punches ( on rotary)

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Fig 12: Compression process principles

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Fig 13 : Compression machine

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Experimental

a. Materials: Granule’s mixture obtained from experiment 2

b. Apparatus/Instrument: analytical balance, Tablet Press Machine, Hardness Tester.
c. Method:
1. Transfer the granules to the compression area
2. Make sure that the compression machine is clean and ready to used
3. Fill the hoper of the machine with the granules
4. Adjust the weight of the tablet
5. Adjust the hardness of the tablets
6. Start compression with the supervision of the responsible person
7. Collect the tablets in plastic bags and transfer them to the storage area

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Results (Report #6)
Take 2 samples of tablets with different compression force and keep the samples in well-
closed container. (30 tablets for each sample )

Fill the following table for the compression process:

Table 14: Lab data during compression process

Time Pressure Machine speed Weight Indicator

Set value Actual Set value Actual Set value Actual

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