Compression and

Compaction
Powders and Tablets
INTRODUCTION
Solid dosage form of medicaments which are meant for internal and external use. Available in amorphous or crystalline
form. Drugs are prepared in different forms and shape but many of them are prepared by using one way or other.

POWDER FLOW PROPERTIES

Pharmaceutical powders may be classified as free flowing or non-free flowing (cohesive). • Flow properties are significantly
affected by changes in: - Particle size, shape, electrostatic charges and adsorbed moisture which may arise from processing
or formulation. • Powder flow should be determined for improvement of pharmaceutical formulation and consequence of
processing.
FLOW RATE
It Is the ratio of mass of the substance to time taken by it to flow” (mass/time) • The flow rate of powder is important
consideration in tableting and other pharmaceutical processes. • Good flow rate will allow efficient movement within the
machines and give good results.
FACTORS AFFECTING POWDER FLOWABILITY
I.PARTICLE SIZE • Frictional + cohesive forces increase as size is decreased resulting in decreased flowability.
II. DENSITY AND POROSITY • Increase density leads to freely flowing powder, decreased porosity leads to freely flowing
powder.
III. PARTICLE SHAPE • Increase in roughness decreases flowability.
IV. PARTICLE SIZE DISTRIBUTION • Increase in amount of fine powder because of compression so that spaces between the
granules can be encamped by the fine powders.
V. MOISTURE CONTENT • Increase in moisture content leads to decrease flowability.
FLOW RATE DETERMINATION

By measuring weight of powder passed through an orifice per time (g/sec) • Variety of orifice size ( ⅛ to ½ inches) should
be made. • Greater standard deviation between flow rate measurements, greater is weight variation in Products. (Not
more than two tablet)
PARTICLE SIZE ANALYSIS (ACCORDING TO USP)
Powders may be course to very fine powders. • Size analysis is done by sieving method in specified time.
COARSE POWDER • Particles pass through No. 20 sieve and not more than 60% through No. 40 sieve.
MODERATELY COARSE POWDER • Particles pass through No. 40 sieve and not more than 60% through No. 60
sieve.
FINE POWDER • Particles pass through No. 80 sieve. No limit as to greater fitness.
VERY FINE POWDER • Particles pass through No. 120 sieve. No limit as to greater fitness.

METHODS FOR DETERMINATION OF PARTICLE SIZE

BY WEIGHT BY VOLUME

• Sieve method • Electronic sensing zone

• Light scattering
• Light scattering
• Optical microscope
• Sedimentation
1. SIEVING
• Sieve Analysis is performed using a nest or stack of sieves where each lower sieve has a smaller aperture size
than that of the sieve above it. • Sieving size range: 5μm – 360mm. • Sieving may be performed wet or dry, by
machine or by hand, for a fixed time or until powder passes through the sieve at a constant low rate.
2. MICROSCOPY
• In this method, small sample size is mounted on the stage of microscope and the particle size is measured
using the micrometer joined to it. • Microscopy size range: 0.2 – 100 Micrometer.
3. SEDIMENTATION
• Determined by measuring setting velocity of particles through liquid medium in gravitational or centrifugal
environment. It can be calculated by Stokes law using Andreasen pipette.
4. LIGHT ENERGY DIFFRACTION
• Disperse particles in liquid/gas, sensing zone determines light reduction.
5. LASER HOLOGRAPHY
• Pulsed laser is fired through an aerosolized particle spray and photographed in 3 dimensions with holographic
camera.
INHERENT PROPERTIES OF POWDERS SOLID AIR INTERFACES
• Atoms or ions located at the surface of any solid particle are exposed to a different distribution of intramolecular and
intermolecular bonding forces than those within the particle. • They may be envisaged as unsatisfied attractive molecular
forces extending out some small distance beyond the solid surface. This condition gives rise to what is called the free surface
energy of the solid, which plays a major role in the interaction between particles, and between a particle and its environment.
• Many important phenomena such as adsorption, cohesion and adhesion, rate of solution, and crystallization are
manifestations of this fundamental property of all solids.
COHESION AND ADHESION • Because of these unsatisfied bonding forces at the surface of particles, those that approach each
other closely enough are inherently attracted and tend to stick to one another. This attraction between like particles is called
cohesion. • In addition, when they approach other types of particles or solid surfaces, they are attracted to them, leading to
what is termed adhesion.
SIGNIFICANCE OF ATTRACTION • These attractions give rise to an intrinsic property of all bulk powdered solids: - They resist
differential movement of their constituent particles when subjected to external forces. • This phenomenon has an important
influence on several operations, such as flow from hoppers or feeders, relative motion in mixers, and compression to produce
granules or tablets.
FACTORS EFFECTING RESISTANCE
The overall resistance to relative movement of particles may be markedly affected by two other factors. - First,
many powders of pharmaceutical interest readily develop electrostatic forces, especially when subjected to
internal friction, although particle contact, and separation are the only prerequisite. The charge developed de-
pends on the particular material involved and the type of motion produced in it. Usually, electrostatic forces are
relatively small, but may be significant because they act over a greater distance than the molecular forces. - The
second factor, namely the presence of an adsorbed layer of moisture on the particles. However, these films of
moisture can form liquid bridges, which hold the particles together by surface tension effects and by a negative
capillary pressure.
ANGLE OF REPOSE
Relatively simple technique to determine flowability of powder. • Qualitative assessment of cohesive and frictional
forces under levels of external loading, applied in powder mixing, in tablet dye or capsule shell filling. • Can be
determined by allowing powder to flow through funnel making heap and then determining height and diameter of
heap. • “Maximum angle obtained between a freely standing surface of powder heap and horizontal surface or
plane”
ANGLE OF REPOSE
FORMULA
𝑇𝑎𝑛θ = 2h D

Where,
- h = heap height of powder cone
- D = powder bed diameter Angle of repose Flow property of powder 40 Poor
DETERMINATION OF ANGLE OF REPOSE
CONE METHOD • A close funnel is fully filled with powder and then inverted on a plain surface and lifted, then from this “h”
and ”D” is measured and calculated by following equation:
𝑇𝑎𝑛θ = 2h D
FIXED FUNNEL METHOD • Take a paper with known width and length. Calculate area by length x width. Adjust funnel on stand
and put that paper under funnel. • Allow 100g powder to flow through funnel. Now, calculate height of heap and encircle the
heap and cut paper. • Now, find grammage:

Grammage = Weight of paper (𝑔) /Area of paper (m2)

• Gram per unit area is necessary for label and cost effectiveness. Now, determine area of cut circular paper by:

Area of cut paper = Weight of circular paper/ Grammage

ROTATING/REVOVING CYLINDER METHOD • The material is placed within a cylinder with at least one transparent face. The
cylinder Is half filled with the test powder. The cylinder is rotated at a fixed speed and the observer watches the material
moving within the rotating cylinder. The granular material will assume a certain angle as it flows within the rotating cylinder
and the angle at which it begins to cascade is noted.

TILTING BOX METHOD • This method is appropriate for fine grained, no cohesive materials,
with individual particle size less than 10mm. The material is placed within a box with a
transparent side to observe the granular test material. It should initially be levelled
and parallel to the base of the box. The box is slowly tilted at a rate of approximately
3 degrees/ second. Tilting is stopped when the material begins to slide in bulk, and the
angle of tilt is measured.
FACTORS AFFECTING ANGLE OF REPOSE • Angle of repose is affected by different coefficients of friction between different
substances. • The size of the particles is a factor. Other factors being equal, fine-grained material will form a shallower pile
with a smaller angle of repose than coarse grains. • Moisture affects the angle of repose. • The method by which the angle of
repose is measured can also affect the measurement.
MASS VOLUME RELATIONSHIP Mass of a bulk powder sample can be determined with great accuracy, measurement of the
volume is more complicated. Three types of air spaces/voids present in powders
I. OPEN INTRA-PARTICULATE VOIDS Those within a single particle but open to the external environment.
II. CLOSED INTRA-PARTICULATE VOIDS • Those within a single particle but closed to the external environment.
III. INTER-PARTICULATE VOIDS • The air spaces be-tween individual particles.

Three interpretations of "powder volume" may be proposed:

I. THE TRUE VOLUME (VT) • The total volume of the solid particles, which excludes all spaces greater than molecular
dimensions, and which has a characteristic value for each material.
II. THE GRANULAR VOLUME (Vg) • The cumulative volume occupied by the particles, including all intraparticulate (but
not inter-particulate) voids.
III. THE BULK VOLUME (Vb) • The total volume occupied by the entire powder mass under the particular packing
achieved during the measurement.
METHODS TO MEASURE
I. HELIUM PYCNOMETER METHOD • Provides nearest approach to true volume. • Within a system containing helium,
change in pressure caused by finite change in volume is the measure of total volume.
II. LIQUID DISPLACEMENT METHOD • To measure granular volume Vg.

DENSITY • The ratio of mass (weight) to volume is known as the density of the material. TYPES • Three different densities for
powdered solids based on following ratios are defined:
I. TRUE DENSITY • It is obtained by dividing mass by true volume of sample
M/ Vt = 𝜌𝑡 the true density
II. GRANULAR DENSITY It is obtained by dividing mass by granular volume.
M/ Vg = 𝜌𝑔 the granular density
III. BULK DENSITY • It is obtained by dividing mass by bulk volume of sample.
M/ Vb = 𝜌𝑏 the bulk density

RELATIVE DENSITY • Comparing the density of sample under specific conditions to true density (sometimes called theoretical
density)
𝜌 𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 = 𝜌(𝑆𝑎𝑚𝑝𝑙𝑒)/ 𝜌(𝑇𝑟𝑢𝑒 𝑑𝑒𝑛𝑠𝑖𝑡𝑦)
During compression process, relative density reaches to maximum of unity (1) as all air spaces are eliminated.
METHOD OF MEASUREMENT BY PYCNOMETER
Wash pycnometer with water and rinse with acetone and air dry it. • Calibrate pycnometer and weigh it. • Fill pycnometer
with given samples one by one. • Then subtract mass of pycnometer from total mass so mass of sample is calculated.

Now, calculate density by formula:

𝐷𝑒𝑛𝑠𝑖𝑡𝑦 = 𝑀𝑎𝑠𝑠 /𝑉𝑜𝑙𝑢𝑚𝑒
GRANULATION
It is a process in which primary powder particles are made to adhere to form larger, multi-
particles entities called granules. It is the process of collecting particles together by creating
bonds between them. Bonds are formed by compression or by using a binding agent.

NEED OF GRANULES
1. TO AVOID POWDER SEGREGATION
Segregation may result in weight variation that is why granules are used to avoid
weight variations.
2. IMPROVE FLOW PROPERTIES OF MIXTURE
Many powders because of small size, irregular shape or surface characteristics
give poor flow but granules improve the flow properties of mixture.
3. IMPROVE COMPACTION CHARACTERISTICS OF MIXTURE
Some powders are difficult to compact so binders are added but granules have
good flowability and produce strong tablets.
4. REDUCE HAZARDS OF TOXIC DUST POWDERS
Hazards of toxic dust powders may arise when handling powders. • By making
granules vibrations are decreased hence stable machinery and no friability.
5. REDUCE HAZARDS OF HYGROSCOPIC POWDERS
On storage, powders may adhere and form cake. • Granulation may reduce this
by absorbing moisture and yet retain their flowability because of size that is why
granules are convenient for storage.
GRANULATION METHODS
Granulation methods can be divided into following types:
1. Dry methods (dry granulation/slugging) - no liquid is used.
2. Wet methods (wet granulation) - use a liquid in the process, binders are added in
solution/suspension form.
3. Direct compression

GRANULATION ADDITIVES
DILUTENTS
To increase bulk, to give unit dose shape, pharmaceutically elegant.
DISINTEGERATING AGENT
To break granules and tablet form before compaction and before granulation.
ADHESIVES
They may also be added in form of dry powders, particularly if dry granulation is employed.
These ingredients will be mixed before granulation.
1. DRY GRANULATION
The dry granulation process is used to form granules without using a liquid solution because
the product to be granulated may be sensitive to moisture and heat. Forming granules
without moisture requires compacting and densifying the powders. In this process the
primary powder particles are aggregated under high pressure.
STEPS IN DRY GRANULATION
I. Compaction of powder
II. Milling
III. Screening
METHOD
The blend of powders are forced into the dies of a large capacity tablet press and is
compacted by means of flat faced pinches, the compacted masses are called slugs, the
process known as slugging. They are then broken into suitable size granules by passing
through an oscillating granulator or sieve no 10, 20 etc. The resultant granules are
mixed with lubricants and other necessary additives. Then they are compressed into
finished tablets in rotatory machine. There are two main processes:
I. SLUGGING
Slugs range in diameter from 1 inch for the more easily slugged material to ¾ inch for
materials that are more difficult to compress and require more pressure per unit area
to yield satisfactory compacts.
II. ROLLER COMPACTOR
The powder is squeezed between two rollers to produce sheet of material (roller
compactor or chilsonator). In both cases these intermediate products are
broken using a suitable milling and sieving technique to produce granular
material, which is usually sieved to separate the desired size fraction. On large
scale, compression granulation can be performed in specially designed
machines. - Chilsonator compactor - Hutt's compactor
ADVANTAGES OF DRY GRANULATION
Avoid heat-temperature combinations that might cause degradation of
products. Best suited for drugs, sensitive to moisture.
2. WET GRANULATION
Wet granulation involves the massing (passing through sieve) of dry primary
powder particles using a granulating fluid. The fluid contain a solvent which may
be volatile so that it can be removed by drying and be non-toxic. Typical liquids
includes water, ethanol and isopropanol, either alone or in combination. The
granulation liquid may be used alone or more usually, as a solvent containing a
dissolved adhesive (binding agent) which is used to ensure particle adhesion
once granules are dry. In the traditional wet granulation method, the wet mass
is forced through a sieve to produce wet granules which are then dried. A
subsequent screening stage breaks agglomerates of granules and removes the
EQUIPMENT USED FOR WET GRANULATION
• High speed mixer granulator • Shear granulators
• Fluidized bed granulators • Spray drier granulators
• Spheronizers/palletizers • Rotor granulators
SHEAR GRANULATORS
Powder mixing in separate operation using suitable mixing equipment. Planetary mixer is used for wet massing
of powder with some formulations such as those containing 2 or 3 ingredients in equal quantities, it is suitable
to mix powder in planetary mixer. • Mixed powders are used. Moist mass is transferred to granulator on
oscillating granulator. Rotor bars of granulator oscillate and force moist mass through sieve screen, size of which
determines granule size. • Mass should be sufficiently moist to form discrete granules when sieved. If excess
liquid is added, string (filament) of material will be formed and if mixture is too dry, mass will be sieved as
powder and granules will not be formed. • Granules can be collected on trays and transferred to drying oven.
Afterwards dry sieving of granules is performed.
HIGH SPEED MIXER-GRANULATOR
The machines have a stainless-steel mixing bowl containing a main impeller, which revolves in
the horizontal plane, and an auxiliary chopper (breaker blade) which revolves either in the
vertical or the horizontal plane. The mixer utilize a bowl. • A high-speed mixer blade revolves
around the bottom of the bowl. The impeller assembly fit over a shaft at the bottom of the
mixing bowl. The impeller assembly is specially constructed to discharge the material from
getting under it. The mixer also contains a high-speed chopper blade which functions as lump
or agglomerate breaker. FLUID BED DRYER • Fluidized-bed granulators have a similar design
and operation to fluidized-bed driers. The powder particles are fluidized in a stream of air, but
in addition granulation fluid is sprayed from a nozzle to the bed of powder.
• Granulating fluid is heated and filtered air is blown or sucked through the bed of unmixed
powder to fluidize the particles and mix the powder; fluidization is actually a very efficient
mixing process. pumped from a reservoir through a spray nozzle positioned over the bed of
particles. The fluid causes the primary powder particles to adhere when the droplets and
powders collide.
3. DIRECT COMPRESSION The materials which are available in crystalline form and have free
flowing and binding characteristics can be compressed directly. But majority of drugs cannot
be compressed easily in this way because sometimes they produce tablets which may not
disintegrate. To overcome this difficulty, directly compressible vehicles such as anhydrous
lactose, compressible sugars are used and then compressed. Drugs which can be directly
compressed are NaCl, NaBr, Na Salicylate. • This method has an advantage of low labor costs
and fewer processing steps.