Complete definition and explanation of powders and granules

• USP- Powders are intimate (close union or combination of particles or
elements) mixtures of dry, finely divided drugs &/or chemicals that may be
intended for internal (oral powders) or external (topical powders/dusting
powders) use.
• Sprowls- Powders are dry mixtures of pulverized (fine particles) drugs or
chemicals intended for internal or external use.

Advantages
1. More effective than tablets, due to small particle size.
2. More stable than liquid dosage form.
3. Less incompatible than liquid dosage form.
4. Large bulky drugs are easily administered in powder form.
5. Easily carried than liquid drugs (portable).
6. Its production is more economical than liquid drugs.
7. Young & old people feel very easy in swallowing powdered drugs than tablets.
8. Can be used for both external & internal uses.
9. Powdered drugs can be added to ointments, pastes, suppositories & other
dosage forms during preparation.
10. Most of the medicinal agents used today are in powder or crystalline form which
are blended by mixing with other powdered materials into solid dosage form.

DISADVANTAGES OF THE POWDER DOSAGE FORM
• Powders have several disadvantages as a dosage form as described below:
1. Patient may misunderstand the correct method of use. Without clear instruction, patients may inhale
through the nose a drug intended for oral administration. In oral administration, it may have to be
clear whether the drug has to be dissolved first in water or taken as is.
2. It is undesirable to take bitter or unpleasant tasting drugs by oral ad
ministration. Many herbal drugs
(mainly infusions in boiling water) have very bitter tastes. To overcome the unpleasant taste of the ex
tracts, it was often told that “bitter medicine is better medicine.” This may not necessarily be true.
3. Bitter, nauseous, corrosive & unpalatable drugs are not dispensed in powder form.
4. It is difficult to protect powders containing hygroscopic, deliquescent (tending to melt or dissolve in
humid environment), or aromatic mate
rials from decomposition.
5. Uniform, individually wrapped doses of powders (sachets) are required and this may increase the
manufacturing expense. (It is possible to in
clude a spoon in a packet of powder drug. This may result
in inaccu
rate amount of drug delivered).
6. Powder must be a homogeneous blend of all of the components and must be of the most
advantageous particle size. The particle size of a drug influences the rate of solubility in water. It may
also influence the biological activity of a drug.

DISADVANTAGES OF THE POWDER DOSAGE FORM…
• 7. volatile oils are not suitable for dispensing in powder form.
• 8. not suitable for administer the potent drugs with a low dose (accuracy)
• 9. not suitable method for the administration of drugs which are inactivated
in, or cause damage to stomach.
• 10. some drugs undergo deterioration in powdered form on exposure to
atmospheric conditions.

• Medicated powders- use is limited
• But the use of powdered substances in the preparation of other dosage form
is extensive, e.g.;
1. Powder drugs may be blended with powdered fillers & other pharmaceutical
ingredients to fabricate solid dosage forms as tablets & capsules.
2. They may be dissolved or suspended in solvents or liquid vehicle to make
various liquid dosage forms.
3. They may be incorporated into semisolid bases in the preparation of
medicated ointments & creams.

• Before the powders used in the preparation of pharmaceutical products;
solid materials first are characterized to determine their chemical &
physical features, including,
• morphology (forms & structure),
• purity,
• solubility,
• flow ability,
• stability,
• particle size,
• uniformity &
• compatibility with any other formulation components.

• Drug and other materials commonly require chemical or
pharmaceutical processing to imbue (inspire or permeate with) the
features desired to enable both the efficient production of a finished
dosage form and the optimum therapeutic efficacy. This usually
includes the adjustment and control of a powder's particle size.

Particle size and analysis
• The particles of pharmaceutical powders and granules may range from being
extremely coarse, about 10 mm (1 cm) in diameter, to extremely fine, approaching
colloidal dimensions of 1 m or less.
• The particle size of powders is standardized according to the USP descrip
tive terms,
such as,
• very fine,
• fine,
• moderately coarse,
• coarse, and
• very coarse.
• which are related to the proportion of powder that is capable of passing through the
openings of standard sieves of varying fineness in a specified period while being
shaken, generally in a mechanical sieve shaker

P.S & Analysis…
• Particle size can inﬂuence a variety of important factors, including the following:
• Dissolution rate of particles intended to dissolve; drug micronization can
increase the rate of drug dissolution and its bioavailability
• Suspendability of particles intended to remain undissolved but uniformly
dispersed in a liquid vehicle (e.g., fine dispersions have particles approximately
0.5 to 10 m)
• Uniform distribution of a drug substance in a powder mixture or solid dosage
form to ensure dose-to-dose content uniformity.
• Penetrability of particles intended to be inhaled for deposition deep in the
respiratory tract (e.g., 1 to 5 m).
• Lack of grittiness of solid particles in dermal ointments, creams, and ophthalmic
preparations (e.g., fine powders may be 50 to 100 m in size)

• A number of methods exist for the determination of particle size, including the
following
1. Sieving, in which particles are passed by mechanical shaking through a
series of sieves of known and successively smaller size and the proportion of
powder passing through or being withheld on each sieve is determined
(range about 40 to 9,500 m, depending upon sieve sizes).

Sieve
• Standard sieve numbers and the openings in each are
expressed in millimeters and in microns.
• Sieves for such pharmaceutical testing and measurement are
generally made of wire cloth woven from brass, bronze, or
other suitable wire.
• They are not coated or plated.

Complete definition and explanation of powders and granules

PARTICLE-SIZE ANALYSIS (How to determine the P.S)
• 1. Sieving
• Sieving is the simplest and probably the most commonly used method for
determining the particle-size distribution. A powder mass is placed on top of a
sifter (mechanical shaker) that is made of a series of screens with se
quentially
smaller apertures. The horizontal sieve motion loosens the packing of particles
allowing subsieve particles to pass through.
• Most widely used screens are woven-wire screens ranging in size starti
ng from
400 openings per inch. In the United States, Tyler standard and US standard
(ASTM E1 1-70) are commonly used. The two standards are different slightly,
but can be used interchangeably.
• American Society for Testing and Materials (ASTM)

American Society for Testing and
Materials (ASTM)

2. Microscopy, in which sample particles are sized through the use of a
calibrated grid background or other measuring device (range 0.2 to 100 m).
• Particle size is measured using a calibrated grid background. The micro
scopic
images of particles can be forwarded to a computer and the size and size
distribution can be analyzed by an image analyzer. The resolution limit by light
microscopy is 0.2 µm. Electron microscopy can be highly useful for the
particles smaller than 0.2 pm.
3. Sedimentation rate, in which particle size is determined by measuring the
terminal settling velocity of particles through a liquid medium in a gravitational
or centrifugal environment (range 0.8 to 300 m). Sedimentation rate may be
calculated from Stokes' law.

• where dx/dt is the rate of settling in cm/s, d is the diameter of the particle in cm, Ps is the
density of the particles (g/cm3
), P0 is the density of the me
dium (g/cm3
), g is the acceleration
due to gravity (981 cm/s2
), and 0 is the viscosity of the medium in poise (g/(cm·s)).
• where
• dx/dt is the rate of settling, dx/dt = d2
(i - e)g / 18
• d is the diameter of the particles,
• i is the density of the particle,
• e is the density of the medium,
• g is the gravitational constant, and
•  is the viscosity of the medium.

• 4. Light energy diffraction or light scattering, in which particle size is
determined by the reduction in light reaching the sensor as the
particle, dispersed in a liquid or gas, passes through the sensing zone
(range 0.2 to 500 m).
• Other automatic particle-size measuring instrument employs the light
scatt
ering principle. This can be performed either in solution or in the
dry powder state.

5. Laser scattering utilizes a He-Ne laser, silicon photo diode detectors, and an
ultrasonic probe for particle dispersion (range 0.02 to 2,000 m).
6. Laser holography, in which a pulsed laser is fired through an aerosolized
particle spray and is photographed in three dimensions with a holographic
camera, allowing the particles to be individually imaged and sized (range 1.4 to
100 m).
7. Cascade impaction, which is based on the principle that a particle driven by
an airstream will hit a surface in its path, provided its inertia is sufficient to
overcome the drag force that tends to keep it in the airstream. Particles are
separated into various size ranges by successively increasing the velocity of the
airstream in which they are carried.
C.Impactors are calibrated at fixed flow rates controlled by a vaccum pump
situated at the out let of the device.

8. Gas Adsorption. The surface area of powdered materials can be measured by
adsorption of solute from solution or of a gas. This method results in the specific
surface area (area/unit mass). Usually, an inert gas, such as nitrogen, is ad
sorbed as a
monolayer and the total volume of gas adsorbed is used to cal
culate the specific
surface area, which in turn provides information on the particle size.
9. Coulter Counter-It determines the volume distribution of particles suspended in an
electrolyte-containing solution. When a particle passes through a small orifice, it
blocks the electric current. The information on particle volume is used for calculating
particle size assuming a spherical shape.
10. Elutriation is a process for separating particles based on their sizes, shape &
density, using a stream of gas or liquid flowing in a direction usually opposite to the
direction of sedimentation. Method mainly used for particles smaller than 1 m.
• These methods and others (centrifugation, permeation, light obstruction) may be
used for the analysis of particle size and shape.

Factors Affected by Particle size
• Particle size can affect a number of factors important to dosage form
preparation as well as applications.
• They are dissolution rate, suspendabil
ity, uniform distribution,
penetrability, and non-grittiness.

• The dissolution rate of particles is dependent on the particle size. The smaller
the particle size, the faster is the dissolution.
• In suspension prepa
ration, it is important to have a good suspendability (i.e.,
ability to main
tain uniform dispersion in liquid vehicle) of particles.
• In a powder mix
ture or capsule and tablets preparation, the ability of a drug to
have uni
form distribution is essential.
• For intrarespiratory applications, the pene
trability of inhaled particles to reach a
desired location within the respira
tory tract is important for deep deposition in
the respiratory tract. The size range of 1–5 µm is widely used.
• In dermal ointments, creams, and oph
thalmic preparations, non-gritty fine
powders should be used. Fine parti
cles of 50–100 µm in size can be used for this
purpose.

Classification of Powders
• Classify on the basis of;
1. Particle size
a) Natural Drugs (vegetable & animal origin)
b) Chemical Drugs (Synthetic drug)
2. Amount of powder
c) Bulk powders
d) Divided powders

a) Natural Drugs- (Powders of vegetable and animal origin drugs) are officially
defined as follows
I. Very coarse powder (No. 8): All particles (100%) pass through a No. 8 sieve
and not more than 20% pass through a No. 60 sieve. (20%/60)
II. Coarse powder (No. 20): All particles (100%) pass through a No. 20 sieve and
not more than 40% pass through a No. 60 sieve. (40%/60)
III. Moderately coarse powder (No. 40): All particles (100%) pass through a No.
40 sieve and not more than 40% pass through a No. 80 sieve. (40%/80)
IV. Fine powder (No. 60): All particles (100%) pass through a No. 60 sieve and
not more than 40% pass through a No. 100 sieve. (40%/100)
V. Very fine powder (No. 80): All particles (100%) pass through a No. 80 sieve.
There is no limit to greater fineness.

b) Chemical Drugs- (Synthetic drugs) are officially defined as follows
I. Coarse powder (No. 20): All particles (100%) pass through a No.
20 sieve and not more than 60% pass through a No. 40 sieve.
(60%/40)
II. Moderately coarse powder (No. 40): All particles (100%) pass
through a No. 40 sieve and not more than 60% pass through a
No. 60 sieve. (60%/60)
III. Fine powder (No. 80): All particles (100%) pass through a No. 80
sieve.
IV. Very fine powder (No. 120): All particles (100%) pass through a
No. 120 sieve.

Amount of Powder
1. Bulk Powders
2. Divided Powders
1. Bulk Powders- These are in the form of bulk & are first prepared by weighing, then milling
& if necessary screening. Bulk Powders dispensed in tight-wide mouth glass container to
afford maximum protection from atmosphere & to prevent the loss of volatile constituents.
• The bulk powder further used to prepared tablets, capsules or to be dispensed in small
amounts in the form of divided powders.
a) Oral Powders
b) Dusting Powders (Medical and Surgical)
c) Dental cleaning Powders
d) Insufflators
e) Douche Powders
f) Trituration Powder

a) Oral Powders
• B.P.- Oral Powders are finely divided powders that contain one or more active
ingredients with or without auxiliary (additional) substances including, where
necessary, authorized flavoring agents & coloring agents/matters.
• They are intended to be taken internally, usually with water or another suitable
liquid.
• Oral powders may also be swallowed directly.
• Oral powders are presented as single dose or multi-dose preparations.
• For single dose powders- each dose is enclosed in a separate container. For
e.g., Sachet or a paper packet
• Multi-dose powder- require the provision of a measuring device capable of
delivering the quantity prescribed.

• Effervescent Oral Powder- presented as single dose or multi dose powder. It
contains acid substances & either carbonates or bicarbonates that reacts
rapidly in the presence of water to release CO2. They are intended to be
dissolved or dispersed in water before administration.
• Oral Rehydration Salt/Powder- containing anhydrous glucose (or glucose),
NaCl, KCl, & either NaHCO3 or sod.citrate.
• Used in oral rehydration therapy
• Also contains suitable flavoring agents
• Oral powders are limited to relatively non-potent drugs such as laxative
(psyllium [Metamucil]), antacids (sodium bicarbonate), dietry supplements
(brewer's yeast powder containing B-complex vitamins and other nutritional
supplements) & certain analgesics.

• Generally, these products are stored at room temperature in a clean, dry
place.
• These products should be kept out of the reach of children and animals.
• Patients should be instructed how to measure the appropriate amount of
the powder and be told the type of liquid or vehicle to use to deliver the
medication consistent with package and/or physician instructions.

b) Dusting Powders
• B.P. dusting Powders are finely divided powders that contain one or more active ingredients
with or without auxiliary (additional) substances including, where necessary, authorized
coloring agents/matters.
• They are free from grittiness.
• They are intended to be applied to the skin for therapeutic, prophylactic or lubricant purposes.
• They are presented as single dose or multi-dose preparations.
• If dusting powder is specifically intended for use on large open wounds or on severely injured
skin, it should be sterile.
• Dusting powders may be presented in pressurized containers, when so presented powders
usually consist of one or more active ingredients held under pressure with suitable propellants
or suitable mixture of propellants. They are delivered by the actuation of an appropriate valve.
• Propellants are either liquefied gases under pressure or compressed gases (Halogenated HCs,
CO2)

• Mixture of these propellants may be used to obtain optimal solution properties
& desirable pressure.
• Dusting powders-presented in pressurized containers may contain suitable
auxiliary substances, such as lubricating agents to prevent clogging of the valve.
• Dusting powders are impalpable (unable to be felt by touch) powders intended for
topical application.
• They may be dispensed in sifter-type containers to facilitate dusting on to the
skin. E.g., cicatrin, talcum powder
• Dusting powder should be passed through at least 10-mesh/sieve to assure
freedom from grit that could irritate traumatized areas.

c) Dental cleaning Powders/ tooth powders
• Dental powders are used in dental hygiene. Dentonic
d) Insufflations (Powder Blowers)
• They are administered in to body cavities (ear, nose, throat, vagina) as such in the form of
decongestant (Nasal Cavity Cleaner). Device Insufflators are used.
• The powder is placed in the vessel. When the rubber bulb is depressed, internal
turbulence disperses the powder and forces it from the orifice.
• Powders may be delivered to various body locations such as the nose, throat, tooth
sockets, or skin.
• Antiseptic powder (clioquinol- Idochlorhydroxyquin),
• antifungal powder,
• antiprotozoal powder,
• Tricromonal- infection of vagina

e) Douche Powder
• These are dissolved in water prior to administration in to the body cavity.
(medicated soln.)
• Douche powders (e.g., Massengill powder), dissolved in warm water by the
patient for vaginal use

COMMINUTION OF DRUGS
• On a small scale, P. size of chemical substances are reduced by grinding with
a mortar and pestle.
• A finer grinding action is accomplished by using a mortar with a rough
surface (as a porcelain mortar) than one with a smooth surface (as a glass
mortar).
• Grinding a drug in a mortar to reduce its particle size is termed trituration
or comminution.

• Levigation is commonly used in small-scale preparation of ointments
and suspensions to reduce the particle size and grittiness of the
added powders.
• A mortar and pestle or an ointment tile may be used.
• A paste is formed by combining the powder and a small amount of
liquid (the levigating agent- Mineral oil and glycerin) in which the
powder is insoluble.
• The paste is then triturated, reducing the particle size.
• The levigated paste may then be added to the ointment base and the
mixture made uniform and smooth by rubbing them together with a
spatula on the ointment tile.

• On a large scale, various types of mills (Fitz Mill) and pulverizers may be used
to reduce particle size.
• In Fitz Mill- particles are reduced in size and passed through a screen of desired
dimension to the collection container. The collection and containment system
protects the environment from chemical dust, reduces product loss, and
prevents product contamination.

Comminution of Drugs/ P.Size Reduction
• Large scale Milling
• Milling
• Milling involves the application of mechanical energy to physically break
down coarse particles to finer ones and is regarded as a “top–down” approach in
the production of fine particles.
• Fine drug particulates are especially desired in formulations designed for
parenteral, respiratory and transdermal use.
• Solids are broken in four different ways: by (1) compression, (2) impact, (3) attrition and (4) cutting. In
general, compression is the main mode for coarse reduction, giving off only few fines, whereas impact can yield
coarse or fine particles and attrition gives extremely fine particles.
• Impact mean pressure exerted by two heavy objects. Attrition: Reduced the size of the materials when they colloid
by heavy weight (Ball)

1.Hammer Mill
• Hammer mills involve feeding solids through a series of spinning hammers contained
within a casing that may also contain breaker plates.
• Attrition of particles is accomplished through their impact with the hammers and the
mill internals. A sieve screen at the mill outlet is used to limit the size of the particle
that can exit the system.
• Hammer mills come in a wide range of motor speeds, and this is the most important
parameter to investigate to ensure reliable scale-up.
• Screen design is another important parameter, in that size and shape of perforations in
the screen will affect mill residence time or how easily milled particles escape the
chamber.
• The hammer mill is not ideal for milling very abrasive materials because significant
metal erosion/mill wear can result over time.
• It is also not preferred for milling highly elastic materials, which could blind the screen,
reduce gas flow through the mill, and lead to overheating.

2.Universal/Pin Mill
• The term universal mill usually refers to a mill configuration where
multiple milling heads can be used.
• These mills often can be fitted with pin, turbo-rotor, and hammer-type
heads.
• Pin mills operate similarly to hammer mills, but with typically faster
rotor speeds and small clearances between rotating and stationary pins.
• These includes two discs with closely spaced pins rotate against one
another at high speeds. Particle size reduction occurs by impaction with
the pins and by attrition (the process of reducing something's strength or effectiveness through sustained attack or pressure)
between pins as the particles travel outwards under the influence of
centrifugal force.

• Solids are fed to a milling chamber in a conveyance gas stream.
• The milling chamber contains a high-speed rotor– stator configuration of pins,
which impact the particles as solids are directed from the center of the pin disc
out through all the rows intermeshing pins.
• Control parameters to adjust and vary the output P.S distribution include pin
gap or pin spacing, the rotational speed of the rotor, solids feed rate, size of the
mill, and velocity of the carrier gas used to convey the solids out of the mill.

3.Ball Mill
• A ball mill is an example of a comminution method which produces size
reduction by both impact and attrition of particles.
• Ball mills consist of a hollow cylinder mounted such that it can be rotated on its
horizontal longitudinal axis.
• The cylinder contains balls that occupy 30% to 50% of the total volume, the ball
size being dependent on the feed and mill size.
• Mills may contain balls with many different diameters as this helps to improve
the process, as the large balls tend to break down.
• Ball mill in operation.
(a) shows rotation
speed too slow,
(b) too fast and
(c) the correct cascade action.

• Coarse feed materials and the smaller balls help to form the fine product by reducing void spaces
between balls.
• The amount of material in a mill is of considerable importance: too much feed produces a cushioning
effect, and too little causes loss of efficiency and abrasive wear of the mill parts.
• The factor of greatest importance in the operation of the ball mill is the speed of rotation. At low angular
velocities (see a) the balls move with the drum until the force due to gravity exceeds the frictional force
of the bed on the drum, and the balls then slide back en masse to the base of the drum.
• This sequence is repeated, producing very little relative movement of the balls, so size reduction is
minimal.
• At high angular velocities (see b), the balls are thrown out to the mill wall, where they remain due to
centrifugal force, and no size reduction occurs.
• At approximately two-thirds of the critical angular velocity where centrifuging occurs (see c), a cascading
action is produced. Balls are lifted on the rising side of the drum until their dynamic angle of repose is
exceeded.
• At this point, they fall or roll back to the base of the drum in a cascade across the diameter of the mill.
• By this means, the most efficient size reduction occurs by impact of the particles with the balls and by
attrition. The optimum rate of rotation is dependent on the mill diameter but is usually of the order of
0.5 revolutions per second.

• Basic fragmentation mechanisms The main idea in modeling all comminution
processes, including the grinding process, is to obtain mathematical relations
between the size of the feed and the size of the product. Particles in the feed
repetitively reduce their size due to the imparting energy of the grinding media
which disrupts their binding forces. The size reduction is a result of the
following three basic fragmentation mechanisms
• − Abrasion occurs when local low intensity stresses are applied and the result
is fine particles taken from the surface of the mother particle and particles of
size close to the size of the mother particle
• − Cleavage of particles occurs when slow and relatively intense stresses are
applied (compression) which produce fragments of size 50-80 % of the size of
the initial particle

• − Fracture is a result of rapid applications of intense stresses (impact)
which produce fragments of relatively small sizes with a relatively
wide particle size distribution
• In practice the three different mechanisms never occur alone and the
process of particle size reduction involves all of them with possible
predominance depending on the type of the mill, the operating
conditions and the type of the material being ground.

4.Vibratory Mill
• The grinding process in vibratory and rotary-vibration mills takes place in a
container called referred to as a chamber.
• In most commonly applied vibratory mills (tube ones) the chamber is a tube
closed on both sides by covers.
• In mills grinding temporarily these are discs whereas in continuously grinding
mills they are perforated discs called riddle baffler which keep the grinding
media in the chamber and provide free flow of the ground material.
• The working grinding elements are grinding media, most frequently of a ball
shape being fed from a vibrating chamber.
• The vibration frequency in classical mills amounts at 17÷25 Hz and the
acceleration of vibrating chamber movement at 60÷300 m/s2

5.Cutter Mill
• A cutter mill consists of a series of knives attached to a horizontal rotor which
act against a series of stationary knives attached to the mill casing.
• During milling, size reduction occurs by fracture of particles between the two
sets of knives, which have a clearance of a few millimeters.
• A screen is fitted in the base of the mill casing and acts to retain material in the
mill until a sufficient degree of size reduction has been effected; thus it is self-
classifying.
• The shear rates present in cutter mills are useful in producing a coarse degree
of size reduction of dried granulations prior to tableting

6.Roller Mill
• A typical roller mill has from one to four pairs of counter rotating rolls mounted
horizontally in a rigid frame, with a feeding device positioned above the top roll pair.
• One roll in each pair is mounted in a fixed position, and the other can be moved closer to
or farther from the fixed roll to adjust the space between the rolls (called the roll gap).
• The roll gap size is based on the desired particle size reduction.
• Roller mills: Precisely reducing particle size with greater efficiency Daniel Ephraim
Modern Process Equipment How the mill works.
• In operation, the feeding device gravity-feeds material at a constant rate to the roll gap
between the top pair of rolls.
• The material enters the nip point (where the gap between the rolls is smallest) and is
crushed into smaller particles as the rolls counter-rotate.
• If the mill has multiple roll pairs, the reduced particles will fall into the next pair’s nip
point, be crushed into smaller particles, and pass to the next roll pair, until the desired
size particles are discharged by gravity from the bottom roll pair

7.Rotary Cutter Mill
• Principle :size Reduction involves successive cutting / Shearing the feed material
with help of sharp knife.
• In this mill, the milling chamber contains 2 types of knives: stationary knives and
rotating knives. A rotor disc is mounted horizontally which consist of 2 to 12 knives
placed at equal distance.
• The rotor disc rotates at a speed of 200-900 rotations per minute.
• The feed is loaded and it comes down due to gravity.
• Due to the rotations made by the rotator disc, the feed material comes in close
contact between the stationary and rotating knives which results in size reduction.
• Small particles pass through the screen while the coarser particles are held again by
the rotating knives and the same procedure is repeated till the desired size is
obtained.
• The shape and size of the particles depends on the size of rotor, gap between rotating
and stationary knives and the opening of sieve.

BLENDING POWDERS
• When two or more powdered substances are to be combined to form
a uniform mixture, it is best to reduce the particle size of each powder
individually before weighing and blending.
• Depending on the nature of the ingredients, the amount of powder,
and the equipment, powders may be blended by;
i. spatulation,
ii. trituration,
iii. sifting, and
iv. tumbling.

• Spatulation is blending small amounts of powders by movement of a spatula
through them on a sheet of paper or an ointment tile.
• It is not suitable for large quantities of powders or for powders containing
potent substances, because homogeneous blending is not as certain as other
methods.
• Very little compression or compacting of the powder results from spatulation,
which is especially suited to mixing solid substances that form eutectic
mixtures (or liquefy) when in close and prolonged contact with one another.
• Substances that form eutectic mixtures when combined include phenol,
camphor, menthol, thymol, aspirin, phenyl salicylate, and other similar
chemicals. To diminish contact, a powder prepared from such substances is
commonly mixed in the presence of an inert diluent, such as light magnesium
oxide or magnesium carbonate, to separate the troublesome agents
physically.

• Trituration may be employed both to comminute and to mix powders.
• If simple admixture is desired without the special need for comminution, the
glass mortar is usually preferred.
• When a small amount of a potent substance is to be mixed with a large amount
of diluent, the geometric dilution method is used to ensure the uniform
distribution of the potent drug.
• This method is especially indicated when the potent substance and other
ingredients are the same color and a visible sign of mixing is lacking.
• By this method, the potent drug is placed with an approximately equal volume
of the diluent in a mortar and is mixed thoroughly by trituration.
• Then, a second portion of diluent equal in volume to the mixture is added and
the trituration repeated.
• This process is continued by adding an equal volume of diluent to the powder
mixture and repeating this until all of the diluent is incorporated.

• Another method of mixing powders is tumbling the powder in a
rotating chamber.
• Special small-scale and large-scale motorized powder blenders mix
powders by tumbling them.
• Mixing by this process is thorough but time consuming.
• Such blenders are widely employed in industry, as are mixers that use
motorized blades to blend powders in a large vessel.

• Segregation is an undesirable separation of the different components of the
blend.
• Segregation may occur by sifting or percolation, air entrapment (ﬂuidization-a
method to keep solid particles floating in an upward direction), and particle entrapment (dusting).
• Fine particles tend to sift or percolate through coarse particles and end up at
the bottom of the container and actually "lift" the larger particles to the
surface.
• Fine, aerated powders with differences in particle size or density may result in
a striation (a pattern of lines or grooves on the surface of something) pattern and may occur during
powder transfer.
• Every process involving the handling of particulate materials with different properties, i.e. particle size,
density, shape or surface roughness can lead to a non-uniform distribution of the particles in the bulk. This
phenomenon is called segregation

• Dusting occurs when the finer, lighter particles remain suspended in air longer
and do not settle as quickly as the larger or denser particles.
• General guidelines to minimize or prevent segregation include
• (a) minimum number of transfer steps and drop heights,
• (b) control of dust generation,
• (c) control of ﬂuidization of the powder,
• (d) slow fill/transfer rate,
• (e) appropriate venting,
• (f ) use of a deﬂector, vane, or distributor,
• (g) proper hopper design and operating valves (if present).

Packaging of Bulk Powder
• Dispensed in tight wide mouth screw cap jar
• Glass Jars- for hygroscopic, deliquescent or volatile products
• Dispensing of bulk powders is limited to non-potent drugs.
• Potent drugs- administered in controlled dosage, usually supplied to patient
in divided amounts.
• Envelops: e.g; cellophane & plastic (poly ethylene envelops)
• As paper packing – time consuming process
• These envelops are usually hydro-resistant
• elegant

2. Divided Powders
• In this case –powder after preparation are divided in to weighed dose.
• This is achieved by 2 methods
a) Weighing method (for potent drug)
b) Block & divide method (for non potent drug)

2. Divided Powders
a) Weighing Method-
• In this method powdered drug is weighed in prescribed dose amount & are
dispensed.
• Method applied for potent drugs.
• Not suitable for divided drugs containing narcotics
b) Block & Divide Method-
• Here, powdered drug is spread evenly on a smooth surface.
• Then equal blocks of powder are made by using spatula.
• Then these blocks are removed separately with the help of spatula.
• Not employed for potent drugs

Packaging of Powders
• The powder papers may be of any size convenient to hold the amount
of powder required, but the most popular commercially available
sizes are, (official sizes of powder paper)
• 2.75 × 3.75 in.,
• 3 × 4.5 in.,
• 3.75 × 5 in., and
• 4.5 × 6 in..

Packaging of Powders
• The papers may be
• (a) simple bond paper; (it is simple white or colored paper, having no moisture
resistant capabilities, commonly preferred for its neat esthetic appearance)
• (b) vegetable parchment, a thin, semi opaque paper with limited moisture
resistance;
• (c) glassine, a glazed, transparent, thin & smooth paper, also with limited Air &
moisture resistance; and
• (d) waxed paper (paraffin paper), a transparent waterproof paper. Not for
baking use, will smoke.

• The selection of the type of paper is based primarily on the nature of the
powder.
• If the powder contains hygroscopic or deliquescent materials, waterproof or
waxed paper should be used. In practice, such powders are double- wrapped
in waxed paper, and then for aesthetic appeal they are wrapped in bond
paper.
• Glassine and vegetable parchment papers may be used when only a limited
barrier against moisture is necessary.
• Powders containing volatile components should be wrapped in waxed or
glassine papers.
• Powders containing neither volatile components nor ingredients adversely
affected by air or moisture are usually wrapped in a white bond paper.

Folding of a powder paper
1. Place the paper flat on a hard surface and fold toward you a uniform flap of
about 0.5 in. of the long side of the paper. To ensure uniformity of all of the
papers, this step should be performed on all the required papers concurrently,
using the first folded paper as the guide
2. With the flap of each paper away and on top, place the weighed or divided
powder in the center of each paper.
3. Being careful not to disturb the powder excessively, bring the lower edge of
the paper upward and tuck it into the crease of the flap
4. Grasp the flap, press it down upon the tucked-in bottom edge of the paper,
and fold again with an amount of paper equal to the size of the original flap (0.5
in.)

5. Pick up the paper with the ﬂap on top, being careful not to disturb
the position of the powder, and place the partially folded paper over
the open powder box (to serve as the container) so that the ends of
the paper extend equally beyond the sides (lengthwise) of the open
container.
Then, press the sides of the box slightly inward and the ends of the
paper gently down along the sides of the box to form a crease on
each end of the paper. Lift the paper from the box and fold the ends
of the paper along each crease sharply so that the powder cannot
escape
6. Place the folded paper in the box so that the double-folded ﬂaps
are at the top, facing you, and the ends are folded away from you.

Medicated Powders
• Some medicated powders are intended to be used internally and others,
externally.
• Most powders for internal use are taken orally after mixing with water or in
the case of infants in their infant formulas.
• Some powders are intended to be inhaled for local and systemic effects.
• Other dry powders are commercially packaged for constitution with a liquid
solvent or vehicle, some for administration orally, others for use as an
injection, and still others for use as a vaginal douche.
• Medicated powders for external use are dusted on the affected area from a
sifter-type container or applied from a powder aerosol.
• Powders intended for external use should bear a label marked external use
only or a similar label.

• Medicated powders for oral use may be intended for local effects
(e.g., laxatives) or systemic effects (e.g., analgesics) and may be
preferred to counterpart tablets and capsules by patients who have
difficulty swallowing solid dosage forms.
• The doses of some drugs are too bulky to be formed into tablets or
capsules of convenient size, so they may be administered as
powders.
• For administration, they can be mixed with a liquid or soft food.
• Powders taken orally for systemic use may be expected to result in
faster rates of dissolution and absorption than solid dosage forms,
because there is immediate contact with the gastric ﬂuids.

• Some medications, notably antibiotics for children, are intended for
oral administration as liquids but are relatively unstable in liquid form.
• They are provided to the pharmacist by the manufacturer as a dry
powder or granule for constitution with a specified quantity of
purified water at the time of dispensing.
• Under labeled conditions of storage, the resultant product remains
stable for the prescribed period of use, generally up to 2 weeks.

Aerosol Powders
• Some medicated powders are administered by inhalation with the aid of dry-
powder inhalers, which deliver micronized particles of medication in
metered quantities.
• Most of these products are used in the treatment of asthma and other
bronchial disorders that require distribution of medication deep in the lungs.
• To accomplish this, the particle size of the micronized medication is
prepared in the range of 1 to 6 m in diameter.
• These products contain inert propellants and pharmaceutical diluents, such
as crystalline alpha-lactose monohydrate, to aid the formulation's ﬂow
properties and metering uniformity and to protect the powder from
humidity

GRANULES
• Granules are prepared agglomerates (collect or form into a mass or group) of smaller
particles of powder.
• They are irregularly shaped but may be prepared to be spherical.
• They are usually in the 4- to 12-mesh sieve size range, although granules of
various mesh sizes may be prepared depending upon their application.
• Granules are prepared by wet methods and dry methods.

• BP: Granules are preparations consisting of solid, dry agglomerates of powder
particles sufficiently resistant to handling. They are intended for oral
administration. Some are swallowed as such, some are chewed and some are
dissolved or dispersed in water or another suitable liquid before being
administered.
• Granules are agglomerates of powdered materials prepared into larger, free
flowing particles. They are usually in the range of 4- to 12-mesh sieve size,
although granules of various mesh sizes may be prepared depending upon their
application. They are irregularly shaped but may be prepared to be spherical.
• Granules contain one or more active ingredients with or without auxiliary
substances including, where necessary, authorized flavoring agents and coloring
matter.
• Granules are presented as single dose or multi-dose preparations.

• Granule Types
• Soluble
• Suspension
• Effervescent

Effervescent Granules
• Effervescent granules are prepared by two general methods:
• (a) the dry or fusion method and
• (b) the wet method.
• In the fusion method, the one molecule of water present in each molecule of
citric acid acts as the binding agent for the powder mixture. Before mixing the
powders, the citric acid crystals are powdered and then mixed with the other
powders of the same sieve size to ensure uniformity of the mixture.
• The mixing of the powders is performed as rapidly as is practical, preferably in
an environment of low humidity to avoid absorption of moisture and a
premature chemical reaction. After mixing, the powder is placed on a suitable
dish in an oven at 34°C to 40°C.

Fusion Method
• During the heating process, an acid-resistant spatula is used to turn the powder.
• The heat releases the water of crystallization from the citric acid, which in turn
dissolves a portion of the powder mixture, setting the chemical reaction and
consequently releasing some carbon dioxide.
• This causes the softened mass of powder to become somewhat spongy, and
when it has reached the proper consistency (as bread dough), it is removed
from the oven and rubbed through a sieve to produce granules of the desired
size.
• A No. 4 sieve produces large granules, a No. 8 sieve prepares medium size
granules, and a No. 10 sieve prepares small granules.
• The granules are dried at a temperature not exceeding 54°C and are
immediately placed in containers and tightly sealed.

Wet Method
• The wet method differs from the fusion method in that the source of binding
agent is not the water of crystallization from the citric acid but the water
added to alcohol as the moistening agent, forming the pliable mass (easily bent;
flexible) for granulation.
• In wet method, all of the powders may be anhydrous as long as water is added
to the moistening liquid.
• Just enough liquid is added (in portions) to prepare a mass of proper
consistency; then the granules are prepared and dried in the same manner as
describe in fusion method.

Preparation of Granules
• Drug+Additives----weighing-----Crushing----- Sieving----- Mixing
(Fillers,disintegrants, Adhesives)-----soft material----- Wet granules---- Dry
Granules---- dosage & package

Mechanism of Granule formation
1. Nucleation- Particle-particle—contact & adhesion due to liquid bridges—join to form---
pendular state
2. Transition– single particles can be added to nuclei by pendular bridge--- two or more nuclei
combine
3. Ball growth—further growth—produce large spherical granules
a) Coalescence– two or more granules join to form a larger granule.
b) Breakage—granules break into fragments which adhere to other granules forming a layers
of material over the surviving granule.
c) Abrasion transfer—agitation of granules bed leads to attrition (the process of reducing something's strength or
effectiveness through sustained attack or pressure) of material from granules. This abraded (scrape) material
adheres to other granules, increasing their sizes.
d) Layering—by spheronizing equipment, when 2nd
batch of powder mix is added to bed of
granules the powder will adhere to the granules, forming a layer over the surface &
increasing the granule size.

Reasons for Granulation
1. To prevent the segregation of the constituents of the powder mix.
2. To improve the flow properties of the mix.
3. To improve the compaction characteristics of the mix.
4. The granulation of the toxic materials will reduce the hazard associated with
the generation of toxic dust that may arise when handling powders.
(granules should be non-friable (not easily crumble) & have a suitable mechanical
strength)
5. Materials which are slightly hygroscopic may adhere & form a cake if stored
as a powder. (Granules will be able to absorb some moisture & yet retain
their flow ability bcoz of their size.)
6. Granules, being denser than the parent powder mix, occupy less volume per
unit weight. (More convenient for storage or shipment)

Complete definition and explanation of powders and granules

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