Powders and Granules

Dr. Mohammad Samir Majzoub

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 Powders
• Advantages and Disadvantages:
• Advantages:
1. More stable than liquid.
2. Suitable for small children and elderly who are unable to swallow,
especially when mixed with milk formula, or juice, and can be sprinkled
on food.
3. Used in blending with medicated application as ointments,
suppositories & pastes.
4. Can be prepared into granules for use in preparing tablets and /or
reconstituted liquid form. Some medications, e.g. antibiotics for
children, are intended for oral administration as liquids but are unstable
in liquid form, provided as a dry powder or granule for constitution
with a specified amount of water.
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 Powders
• Advantages and Disadvantages:
• Advantages:
5. Rapid therapeutic effect, it requires only dissolution not disintegration
before absorption.
6. Physician can readily adjust the dose.
7. 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.
8. Easier to carry than the liquid dosage forms.

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 Powders
• Advantages and Disadvantages:
• Disadvantages:
1. Undesirability of taking (bitter or unpleasant tasting of drugs).
2. Difficulty of protecting from decomposition (powders containing
hygroscopic, deliquescent or aromatic materials).
3. Time and expenses require in the preparation of uniform powders.
4. Inaccuracy of bulk powders.

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 Powders
• Types of powders:
• Medicated Powders:
1. Medicated powders are intended to be used internally & externally.
2. Most powders for internal use are taken orally after mixing with water
as in infant formulas.
1. Some powders are intended to be inhaled for local and systemic effects.
2. 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.
3. Medicated powders for external use are dusted on the affected area
from a sifter-type container or applied from a powder aerosol.
4. Medicated powders for oral use may be intended for local effects (e.g.,
laxatives) or systemic effects (e.g., analgesics).
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 Powders
• Types of powders:
• Aerosol Powders:
1. Some medicated powders are administered by inhalation with the aid of
dry-powder inhalers (DPI), which deliver micronized particles of
medication in metered quantities.
2. 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 μm in diameter.

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 Powders
• Types of powders:
• Aerosol Powders: dry-powder inhalers (DPI)

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 Powders
• Types of powders:
• Aerosol Powders:
3. In addition to the therapeutic agent, 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. Powder
blowers or insufflators may be used to deliver dry powders to various
parts of the body, e.g., nose, throat, lung, vagina.

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 Powders
• Types of powders:
• Bulk and Divided Powders:
A. Bulk Powders:
1. Among the bulk powders available in prepackaged amounts are:
a. Antacids (e.g., Na-bicarbonate) & laxatives (e.g., psyllium [Metamucil]),
which the patient takes by mixing with water or another beverage before
swallowing.
b. Douche powders (e.g., Massengill powder- Cleansing Douche for Hygenic
Purposes), dissolved in warm water by the patient for vaginal use.
c. Medicated powders for external application to the skin, usually topical
anti-infectives (e.g., bacitracin zinc & polymyxin B sulfate) or antifungals
(e.g., tolnaftate).
d. Brewer’s yeast powder containing B-complex vitamins & other nutritional
supplements. 10
 Powders
• Types of powders:
• Bulk and Divided Powders:
A. Bulk Powders:
2. In some cases, a small measuring scoop, spoon, or other device is
dispensed with the powder for measuring the dose of the drug.
3. Dispensing powder medication in bulk quantities is limited to non-
potent substances.
4. Powders containing substances that should be administered in
controlled dosage are supplied to the patient in divided
amounts in folded papers or packets.

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 Powders
• Types of powders:
• Bulk and Divided Powders:
A. Bulk Powders:
5. EX: Dusting powders, Medicated or non-medicated powders,
Dentifrices or dental cleansing powders, Insufflations (Are finely
divided powders introduced into the body cavities such as the ears, nose,
throat, tooth sockets and vagina).
6. These powders should be stored at room temperature in a
clean, dry place. And patient should be instructed about the type of
liquid or vehicle to use to deliver the medication.

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 Powders
• Types of powders:
• Bulk and Divided Powders:
B. Divided Powders:
1. After a powder has been properly blended (using the geometric dilution
method for potent substances), it may be divided into individual dosing
units based on the amount to be taken or used at a single time.
2. Each divided portion of powder may be placed on a small piece of paper
that is folded to enclose the medication.
3. A number of commercially prepared premeasured products are available
in folded papers or packets, including :
1. Headache powders.
2. Powdered laxatives (e.g., psyllium mucilloid, cholestyramine resin)
3. Douche powders (e.g., Massengill powder packets).
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 Powders
• Types of powders:
• Bulk and Divided Powders:
B. Divided Powders:
4. Divided powders may be prepared by the pharmacist as follows. Depending
on the potency of the drug substance, the pharmacist decides whether to:
a. Weigh each portion of powder separately before enfolding in a paper (potent).
b. Use the block-and-divide method:
i. Used only for non-potent drugs.
ii. The pharmacist places the entire amount of the prepared powder on a flat surface such as
a porcelain or glass plate, pill tile, or large sheet of paper and, with a large spatula,
forms a rectangular or square block of the powder having a uniform depth. Then, using
the spatula, the pharmacist cuts into the powder lengthwise & crosswise to delineate
the appropriate number of smaller, uniform blocks, each representing a dose or unit of
medication. Each of the smaller blocks is separated from the main block with the spatula,
transferred to a powder paper, and wrapped.
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 Powders
• Types of powders:
• Bulk and Divided Powders:
B. Divided Powders:
5. The Papers May Be:
a. Simple bond paper.
b. Vegetable parchment paper, a thin, semi opaque paper with limited
moisture resistance.
c. Glassine, a glazed, transparent paper, also with limited moisture
resistance.
d. Waxed paper, a transparent waterproof paper.

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 Powders
• Types of powders:
• Bulk and Divided Powders:
B. Divided Powders:
6. The Selection of the Type of Paper is Based Primarily on the Nature of
the Powder:
a. 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, & then for aesthetic appeal they are wrapped in bond paper.
b. Glassine and vegetable parchment papers may be used when only a limited
barrier against moisture is necessary.
c. Powders containing volatile components should be wrapped in waxed or
glassine papers.
d. Powders containing neither volatile components nor ingredients adversely
affected by air or moisture are usually wrapped in a white bond paper.
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 Powders
• Types of powders:
• Topical powders:
• Should have:
1. Uniform, small particle size.
2. No skin irritation.(should be passed through at least a No. 100 mesh sieve)
3. Impalpable (unable to be felt by touch) and free flowing.
4. Easily adhere to the skin.
• A hydrophobic powder, rather than a highly sorptive one, should be
applied to oozing (discharging) wound, because the first will prevent loss
of water from the skin, and will not cake on the oozing surface.

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 Powders
• Types of powders:
• Insufflated powders:
1. Finely divided powders, that are intended to be applied in a body
cavity, such as the ears, nose, vagina, tooth socket, or throat.
2. A moisture-activated adherent, such as polyox, can be incorporated
into the powder.
3. Polyox is an ethylene oxide polymer with a high molecular weight
that forms a viscous, muco-adhesive gel when in contact with
moisture.
4. Gel serves to provide a depot for long term drug delivery spanning
several hours.

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 Powders
• Examples of Bulk Powders:
1. Antacid or laxative powders, which the patient generally takes by
mixing the directed amount of powder.
2. Douche powder usually dissolved in warm water by the patient
for vaginal use.
3. Dusting powders.
4. Medicated or non-medicated powders.
5. Dentifrices or dental cleansing powders.
6. Insufflations.
7. Triturations.

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 Powders
• Douche Powders:
• Are products which are completely soluble and are intended to be
dissolved in water prior to use as antiseptic or cleansing agent for
a body cavity.
• Simply add the prescribed amount or powder to the appropriate
volume of warm water and stirs until dissolved.
• Packaging: may be in a wide mouth glass jars to protect from
volatile constituents and by bulk powder boxes.

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 Powders
• Chemical and Physical Properties:
Before their use in the preparation of pharmaceutical products, solid
materials first are characterized to determine their chemical and physical
features, including:
1. Morphology (spherical and oval powders flow more easily than
needle-shaped powders and make processing easier).
2. Purity (the purity of the chemical substance is essential for its
identifications, and for evaluation of its physical, chemical, and
biological properties).
3. Solubility (for a drug to enter the systemic circulation and exert a
therapeutic effect, it must first be in solution. Insoluble compounds
often exhibit incomplete, or erratic absorption).

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 Powders
• Chemical and Physical Properties:
Before their use in the preparation of pharmaceutical products, solid
materials first are characterized to determine their chemical and physical
features, including:
4. Flowability (good flow properties make processing easier)
5. Stability (physical and chemical stability)
6. Particle size.
7. Uniformity (depends on particle size and the equal distribution of
the active ingredients throughout the formulation)
8. Compatibility with any other formulation components.

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 Powders
• Factors Affected by Particle Size:
• The particles of pharmaceutical powders may range from
extremely coarse (10cm), to extremely fine (1µm)
• USP uses these descriptive terms 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.

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 Powders
• Factors Affected by Particle Size:

Very coarse (No.8): All particles pass through a No. 8 sieve & not more than 20% through a No. 60
sieve.
Coarse (No. 20): All particles pass through a No. 20 sieve & not more than 40% through a No. 60
sieve.
Moderately coarse (No. 40): All particles pass through a No. 40 sieve & not more than 40%
through a No. 80 sieve.
Fine (No. 60): All particles pass through a No. 40 sieve & not more than 40% through a No. 100
sieve
Very Fine (No. 80): All particles pass through a No. 80 sieve. There is no limit to greater fineness.

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 Powders
• Factors Affected by Particle Size:
• Particle size can influence a variety of important factors, including the
following:
1. Dissolution rate of particles intended to dissolve.
2. Suspendability of particles intended to maintain uniform dispersion in
liquid vehicle.
3. Uniform distribution of a drug substance in a powder mixture or solid
dosage form to ensure dose-to-dose content uniformity.
4. Penetrability of particles intended to be inhaled for deposition deep in the
respiratory tract (e.g., 1 to 5 μm).
5. Lack of grittiness of solid particles in dermal ointments, creams, and
ophthalmic preparations (e.g., fine powders may be 50 to 100 μm in size).

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 Powders
• Particle Size Analysis and Method of Determining Particle Size:
• A number of methods exist for the determination of particle size:
1. Sieving, in which particles are passed by mechanical shaking through a
series of sieves of known & successively smaller size and the proportion
of powder passing through or being withheld on each sieve is
determined (range about 40 to 9,500 μm, depending upon sieve sizes).
2. Microscopy, sample particles are sized through the use of a calibrated
grid background or other measuring device (range 0.2 to 100 μm).
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 μm).
Sedimentation rate may be calculated from Stokes’ law.

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 Powders
• Particle Size Analysis and Method of Determining Particle Size:
• A number of methods exist for the determination of particle size:
3. Sedimentation rate:

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 Powders
• Particle Size Analysis and Method of Determining Particle Size:
• A number of methods exist for the determination of particle size:
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 μm).
5. 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 100μm).

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 Powders
• Particle Size Analysis and Method of Determining Particle Size:
• A number of methods exist for the determination of particle size:
6. Cascade impaction, which is based on the principle that a particle driven
by an air-stream 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.
7. Coulter Counter 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.
https://www.youtube.com/watch?v=HZ3Xb3g5XKU
https://www.youtube.com/watch?v=nrxNzf08VCc
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 Powders
• Comminution (Particle Size Reduction):
Comminution is the action of reducing a material to minute particles or
fragments.
1. Trituration: On a small scale, the pharmacist reduces the size of chemical
substances by grinding with a mortar & 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).

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 Powders
• Comminution (Particle Size Reduction):
2. Pulverization by Intervention: Is the reduction of particle size with the
aid of a 2nd agent which can be readily removed from the pulverized
product. https://www.youtube.com/watch?v=r9QAqXIBT1I
3. Levigation:
a. Commonly used in small-scale preparation of ointments &
suspensions to reduce particle size & grittiness of added powders.
b. 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) in which the powder is insoluble.

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 Powders
• Comminution (Particle Size Reduction):
3. Levigation:
c. 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.
d. Mineral oil and glycerin are commonly used levigating agents.
e. The Basis of Choice of Levigating Agent is:
• Its ability to form a smooth paste with the substance.
• Its compatibility in the product (ex: water cannot be used for
levigating a substance for oleaginous ointment base).

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 Powders
• 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:
1. Spatulation,
2. Trituration,
3. Sifting and
4. Tumbling.

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 Powders
• Blending Powders:
1. Spatulation:
a. Is blending small amounts of powders by movement of a spatula
through them on a sheet of paper or an ointment tile.
b. 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.
c. 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 & prolonged
contact with one another.

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 Powders
• Blending Powders:
1. Spatulation:
c. Eutectic mixtures:
• 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 with a bulky powder adsorbent such as; light
magnesium oxide or magnesium carbonate, to separate the
troublesome agents physically.
• These powders should be triturated very lightly.
• Dispense the ingredients separately.

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 Powders
• Blending Powders:
2. Trituration:
a. May be employed both to comminute and to mix powders.
b. If simple admixture is desired without the special need for
comminution, the glass mortar is usually preferred.
c. 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.

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 Powders
• Blending Powders:
2. Trituration:
d. Geometric dilution:
1. This method is especially indicated when the potent substance and other
ingredients are the same color and a visible sign of mixing is lacking.
2. 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.
3. Some pharmacists add an inert colored powder to the diluent before mixing
to permit visual inspection of the mixing process.

37
 Powders
• Blending Powders:
2. Trituration:
e. Potent Drug:
1. Problem: Limited precision and accuracy of the used balances to weight
small amounts of potent drugs.
2. Solution: Drug triturates:
i. Suitable diluents like lactose are mixed with the potent drug to form
10% w/w drug triturates.
ii. Very fine powders should be used in the triturates.
iii. Geometric dilution to prepare drug triturates.

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 Powders
• Blending Powders:
2. Trituration:
f. Incompatible salts:
1. Problem: Chemically incompatible salts when triturated together produce
discoloration, chemical deterioration or loss of potency.
2. Solution:
i. Compounding such substances with minimum pressure.
ii. Use a convenient method for mixing the powder like tumbling
(dropping) in a jar or spatulation on a sheet of paper.
iii. Each substance should be powdered separately in a clean mortar and
then combined with other ingredients gently.
iv. Powder and dispense separately.

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 Powders
• Blending Powders:
3. Sifting:
• Powders may also be mixed by passing them through sifters (sieves) like
those used in the kitchen to sift flour. Sifting results in a light, fluffy
product. This process is not acceptable for the incorporation of potent
drugs into a diluent powder.
4. Tumbling:
• Is the process of mixing powders by placing in large containers or
powder blenders that rotates by tumbling motion. Mixing by this process
is thorough but time consuming.

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 Powders
• Hygroscopic and deliquescent powders:
1. Hygroscopic powders will absorb moisture from the air.
2. Deliquescent powders will absorb moisture from the air to the extent
that they will wholly or partially liquefy.
3. EX: amonium bromide, lithium bromide, hyoscyamine hydrobromide….
4. Solution: dispense the ingredients in tight containers and incorporate a
desiccant (drying) packet or capsule when necessary.
5. Patient should be instructed to store the powder in a dry place in a
tightly closed container.

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 Powders
• Efflorescent powders:
1. Crystalline powder that contains water of hydration or crystallizations.
This water can be liberated either during manupilations or on exposure
to a low-humidity environment.
2. If this occurs, the powder will become sticky and pasty, or it may even
liquify.
3. EX: alums, caffeine, citric acid, codeine sulfate, cocaine, ferrous
sulfate…..
4. Soultion: use anhydrous salt form of the drug, or include a drying bulky
powder, and to use a light, noncompacting method of mixing the
powders.

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 Granules
• Definition of Granules:
Granules are prepared agglomerates 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.

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 Granules
• Advantages of Granules Over Powders:
1. Granules are more flowable compared to powders. Because of their
flow properties, granulations are commonly used in tablet making to
facilitate the free flow of material from the feeding container (or
hopper) into the tablet presses.
2. Segregation of the constituents of the powder mixture could be
avoided by granulation. Segregation occurs due to difference in particle
size or densities (small particles and denser particles concentrated in the
base of the container and vice versa), by granulation same particles i.e.
narrow range of p.s. distribution, so that no segregation).

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 Granules
• Advantages of Granules Over Powders:
3. Because their surface area is less than that of a comparable volume of
powder, granules are usually more stable to the effects of atmospheric
humidity and are less likely to cake or harden upon standing.
4. Granules are more easily wetted by liquids than light and fluffy
powders (which tend to float on the surface) and are more preferable
for dry products intended to be constituted into solution or suspension
(mostly antibiotics for stability reasons).

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 Granules
• Reasons for Granulation: To improve the flow properties of the mix
a. Many powders, because of their small size, irregular shape or surface
characteristics, are cohesive and do not flow well.
b. Poor flow will often result in a wide weight variation within the final
product owing to variable fill of tablet dies etc.
c. The granulation of toxic materials will reduce the hazard associated
with the generation of toxic dust that may arise when handling
powders.
d. Materials which are slightly hygroscopic may adhere and form a cake
if stored as a powder.
e. Granules, being denser than the parent powder mix, occupy less
volume per unit weight. They are therefore more convenient for
storage or shipment.
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 Granules
• Examples of Commercial Products:
1. Products containing antibiotic drugs that are unstable in
aqueous solution are prepared as small granules for constitution
by the pharmacist with purified water just prior to dispensing.
2. The granules are prepared to contain not only the medicinal
agent but also colorants, flavorants, and other pharmaceutical
ingredients.
3. Upon constitution, the resultant liquid has all of the desired
medicinal & pharmaceutical features of a liquid pharmaceutical.
4. The granules are measured and mixed with water or another
beverages, sprinkled on food, or eaten plain.

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 Granules
• Preparation of Granules:
Granules are prepared by wet methods and dry methods.
1. One basic wet method is to moisten the powder or powder mixture and
then pass the resulting paste through a screen of the mesh size to
produce the desired size of granules.
2. The granules are placed on drying trays & are dried by air or under heat.
3. The granules are periodically moved about on the drying trays to
prevent adhesion into a large mass.
4. Another type of wet method is fluid bed processing, in which particles
are placed in a conical piece of equipment and are vigorously dispersed
and suspended while a liquid excipient is sprayed on the particles and
the product dried, forming granules or pellets of defined particle size.
https://www.youtube.com/watch?v=QYFe0SAbvH0 - https://www.youtube.com/watch?v=2wVQ69Wz39s
48
 Granules
• Preparation of Granules:
1. Wet Granulation:

49
 Granules
• Preparation of Granules:
1. Wet Granulation:
Wet granulation is widely employed method for the production of
compressed tablets. The steps required for the wet granulation can be
divided into following stages:
a. Weighing and blending the ingredients.
b. Preparing the wet granulation.
c. Screening the damp (moist) mass into granules.
d. Drying the granules.
e. Sizing the granules by dry screening.
f. Lubricating and blending.
g. Tablet by compression.
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 Granules
• Preparation of Granules:
1. Wet Granulation:
• Fillers include:
1. Lactose
2. Cellulose derivatives
3. Starch
4. Powdered sucrose
5. Calcium phosphate
• Disintegrating agent used includes:
1. Corn and potato starch
2. Cellulose derivatives.

51
 Granules
• Preparation of Granules:
1. Wet Granulation:
• Preparing the wet granulation:
1. Granulation is accomplished by adding liquid binder or adhesive to the powder.
2. The wet mass is then passed through the screen of desired mesh size.
3. The granules so obtained are dried.
4. Then again they are passed though a second screen of smaller mesh size to
further reduce the size of the granules.
5. The binding agent used are
• 10-20% aqueous preparations of corn starch.
• 25-50% solution of glucose.
• Natural gums (acacia)
• Cellulose derivatives (methylcellulose, carboxy methylcellulose)
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 Granules
• Preparation of Granules:
1. Wet Granulation:
• Screening the damp (moist) mass into granules:
1. The wet granulation is pressed through a No. 6 or 8 mesh size.
2. This may be done with hand or special machines.
3. The resultants granules are spread evenly on large paper in shallow
(superficial) trays and dried.
• Drying the granules:
1. The granules are dried in drying cabinets that have circulating air systems
and are thermostatically controlled.
2. Among the newer methods employed for the drying is fluidization
conducted in fluid bed drier.

53
 Granules
• Preparation of Granules:
1. Wet Granulation:
• Sizing the granules by dry screening:
1. The degree to which the granules are reduced depends upon the size of
the punch and tablet to be produced.
2. The smaller tablet size, smaller the granules used.
3. Sizing of the granules is important so that die cavity for tablet compression
is fully filled with granules.
4. The voids are air spaces could result in uneven tablet.

54
 Granules
• Preparation of Granules:
1. Wet Granulation:
• Lubrication:
1. After dry screening, dry lubricant is generally added.
2. The more commonly used lubricants are: Talc, Magnesium stearate,
Calcium stearate.
3. Range at which it is added is from as low as 0.1% to 5% of the weight of the
granulation.

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 Granules
• Preparation of Granules:
1. Wet Granulation:
• Limitation of wet granulation:
1. The greatest disadvantage of wet granulation is its cost. It is an expensive
process because of labor, time, equipment, energy and space requirements.
2. Loss of material during various stages of processing
3. Stability, major concern for moisture sensitive or thermo labile drugs.
4. Multiple processing steps add complexity and make validation
and control difficult
5. An inherent limitation of wet granulation is that any incompatibility
between formulation components is aggravated (intensified).
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 Granules
• Preparation of Granules:
2. Dry Granulation:
a. The dry granulation method may be performed in a couple of ways. By
one method, the dry powder is passed through a roll compactor and
then through a granulating machine. https://www.youtube.com/watch?v=QYwGpEqAqlQ
b. A roll compactor, also called a roll press processes a fine powder into
dense sheets or forms by forcing it through two mechanically rotating
metal rolls running counter to each other.
c. The surface of the compacting rolls may be smooth or may have pocket
indentations (depressions) or corrugations that allow compaction of
different forms and textures.
d. The compacted powder is granulated to uniform particle size in a
mechanical granulator.
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 Granules
• Preparation of Granules:
2. Dry Granulation:
e. Powder compactors are generally combined in sequence in integrated
compactor–granulation systems.
f. An alternative dry method, termed slugging, is the compression of a
powder or powder mixture into large tablets or slugs on a compressing
machine under 8,000 to 12,000 lb of pressure, depending on the
physical characteristics of the powder.
https://www.youtube.com/watch?v=IzbpA7HWIeg https://www.youtube.com/watch?v=IzbpA7HWIeg

g. The slugs are generally flat-faced and are about 2.5 cm (1 in.) in
diameter. The slugs are granulated into the desired particle size,
generally for use in the production of tablets.
h. The dry process often results in the production of fines (powder that
has not agglomerated into granules).
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 Granules
• Preparation of Granules:
2. Dry Granulation:
i. The wet and dry granulation methods are followed for tablet making.
j. A number of commercial products containing antibiotic drugs that are
unstable in aqueous solution are prepared as small granules for con-
stitution by the pharmacist with purified water just prior to dispensing.
The granules are prepared to contain not only the medicinal agent but
also colorants, flavorants, and other pharmaceutical ingredients.

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 Granules
• Preparation of Granules:
2. Dry Granulation:
k. Other types of granulated commercial products include Lactinex
granules, a mixed culture of Lactobacillus acidophilus and Lactobacillus
bulgaricus in 1-g packets used in the treatment of uncomplicated
diarrhea and diarrhea due to antibiotic therapy.
l. The granules are measured & mixed with water or another beverages,
sprinkled on food, or eaten plain.

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 Granules
• Preparation of Granules:
2. Dry Granulation:
• Steps in dry granulation:
a. Milling (Grinding) of drugs and excipients.
b. Mixing of milled powders.
c. Compression into large, hard tablets to make slug.
d. Screening of slugs.
e. Mixing with lubricant and disintegrating agent.
f. Tablet compression.

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 Granules
• Preparation of Granules:
2. Dry Granulation:
• Advantages:
1. The main advantages of dry granulation or slugging are that it uses less
equipments and space.
2. It eliminates the need for binder solution, heavy mixing equipment &
the costly & time consuming drying step required for wet granulation.
3. Slugging can be used for advantages in the following situations:
a. For moisture sensitive material
b. For heat sensitive material
c. For improved disintegration since powder particles are not bonded
together by a binder.
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 Granules
• Preparation of Granules:
2. Dry Granulation:
• Disadvantages:
1. It requires a specialized heavy duty tablet press to form slug.
2. It does not permit uniform color distribution as can be achieved with
wet granulation where the dye can be incorporated into binder liquid.
3. The process tends to create more dust than wet granulation, increasing
the potential of contamination.

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 Granules
• Effervescent Granules:
• They are granules of drug in a dry mixture usually composed of
Sodium bicarbonate, Citric acid and Tartaric acid, when added to
water, the acids and the base react to liberate CO2, resulting in
effervescence.
• Why a Combination of Tartaric Acid and Citric Acid is Used as an
Effervescent Base Rather Than Either Acid Alone?

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 Granules
• Effervescent Granules:
• When added to water, the acids and the base react to liberate
carbon dioxide, resulting in effervescence.
• The resulting carbonated solution masks undesirable taste of any
medicinal agent.
• Using granules or coarse particles of the mixed powders rather
than small powder particles decreases the rate of dissolution and
prevents violent and uncontrollable effervescence.
• Sudden and rapid effervescence could overflow the glass & leave
little residual carbonation in the solution.

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 Granules
• Effervescent Granules:

• Using a combination of citric and tartaric acids rather than either acid
alone avoids certain difficulties. When tartaric acid is used as the sole
acid, the resulting granules readily lose their firmness and crumble. Citric
acid alone results in a sticky mixture difficult to granulate.
• Disadvantages of Effervescent Granules:
1. Instability in presence of moisture.
2. Problems in packaging and storage.
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 Granules
• Effervescent Granules:
• Preparation of Effervescent Granules: Effervescent granules are
prepared by two general methods:
1. Dry or Fusion Method:
a. 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.
b. 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.
c. The sieves and the mixing equipment should be made of stainless steel
or other material resistant to the effect of the acids.

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 Granules
• Effervescent Granules:
• Preparation of Effervescent Granules: Effervescent granules are
prepared by two general methods:
1. Dry or Fusion Method:
d. 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.
e. After mixing, the powder is placed on a suitable dish in an oven at 34°C
to 40°C. During the heating process, an acid- resistant spatula is used to
turn the powder.

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 Granules
• Effervescent Granules:
• Preparation of Effervescent Granules: Effervescent granules are
prepared by two general methods:
1. Dry or Fusion Method:
f. Heat releases the water of crystallization from citric acid, which in turn
dissolves a portion of the powder mixture, setting the chemical reaction
& consequently releasing some carbon dioxide. This causes the softened
mass of powder to become somewhat spongy, & when it has reached
the proper consistency (as bread dough-paste), it is removed from the
oven & rubbed through a sieve to produce granules of desired size.

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 Granules
• Effervescent Granules:
• Preparation of Effervescent Granules: Effervescent granules are
prepared by two general methods:
1. Dry or Fusion Method:
g. 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.

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 Granules
• Effervescent Granules:
• Preparation of Effervescent Granules: Effervescent granules are
prepared by two general methods:
2. Wet Method:
a. 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 (flexible) mass for granulation.
b. In this method, all of the powders may be anhydrous as long as water
is added to the moistening liquid.
c. 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 described.
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