Technology of Solid Dosage Forms &Disperse
Systems
by/
Dr. Mekaiel Amiel Mekaiel M.Sc. Pharmaceutical Technology
Powders & Granules
Learning outcomes
By the end of this session student should be able to:
1. Define pharmaceutical powders.
2. Explain the detailed formulation and manufacturing unit operation involved in the manufacture of pharmaceutical powders.
3. Identify the excipients used and their role/function in the formula.
4. Describe different powder dosage forms and its uses.
5. Describe different techniques employed in production of powders.
6. Differentiate and compare between different types of powders.
TOPIC CONTENTS:
Powder: a) Introduction
b) Classification
c) Mixing of powders
d) Method of preparation
e) Advantages and disadvantages
f) Shelf life and storage
g) Containers
h) Packaging
i) Labeling
j) Pharmaceutical uses
Introduction
Powders are dry mixtures of finely
divided medicinal and nonmedicinal
agents intended for internal or external
use. Powders may be dispensed in bulk
form, or they may be divided into single-
dosage units and packaged in folded
papers or unit-of-use envelopes.
Definition:
Classification of Powders:
(a)Classification on the basis of use:
1)Bulk powder for internal use
2)Bulk powder for external use
3)Divided or unit doses powder
1).Bulk powder for internal use
• They are mixture of finely divided drugs
and\ or chemicals in a dry form that may be
intended for internal use (oral powders)
Types:
a) Oral powder
b) Powder spray
c) Dry powder inhalers
d) Effervescent powders
2).Bulk powder for external use
• They are mixtures of finely divided drugs
and/ or chemicals in a dry form that may be
intended for external use available in
multiple doses (dusting powder)
Types:
a) Dusting powders
b) Insufflations
c) Dentifrices
3) Divided powder
• Divided powder are similar formulation to
bulk powder but individual doses are
separately wrapped.
Types
a) Douche powders
b) Powder for injection
c) Effervescent powders
Size classification of powders
Particle size Analysis
The powders have been classified into:
i. Very coarse (#8): All particles pass through sieve
no.8 and not more than 20% through sieve no.20
ii. Coarse (#20): All particles pass through sieve no.20
and not more than 40% through sieve no.60
iii. Moderate (#40): All particles pass through sieve
no.40 and not more than 40% through sieve no.60
iv. Fine (#60): All particles pass through sieve no.60
and not more than 40% through sieve no.80
v. Very fine: All particles pass through this sieve.
There is no limits as greater fineness.
Mixing of powders
• Ingredients of powder should be mixed
thoroughly using the technique of doubling-up
to insure an even distribution(some times
called geometric dilution).
• This process involves starting with ingredient
which has smallest bulk.
• The other ingredients are added progressively
in approximately equal parts by volume.
• In this way the amount in the mortar is
approximately doubled at each addition.
Mixing of powders
• Mixing in b.w additions continues
until all the ingredients are
incorporated. The powder can then be
packed.
Method of preparation
1. Reduction of particle size of all
ingredients to the same range to prevent
stratification.
2. Sieving.
3. Weighing of each ingredient.
4. Mixing.
5. Packaging.
(a)General method for preparation of
bulk powders:
1. Weigh the powder present in smallest
volume (powder A) and placed in
mortar.
2. Weigh the powder present in the next
largest volume (powder B) and placed
on labeled weighing paper.
3. Add approximately same amount of
powder B as powder A in the mortar.
Cont.
4. Mix well with pestle.
5. Continue adding amount of powder B
that is approximately the same as that in
the mortar and mix with the pestle, i.e
doubling the amount of powder in the
mortar at each addition.
(b)General method for preparation
of divided powders:
1. The minimum weight of individually wrapped
powder is 120mg.Dilution of drug with a
diluent usually lactose is often necessary to
produce this weight.
2. Usually tablets or capsules may be used to
prepare oral powders . This involves either
crushing the tablets in a mortar and pestle, or
emptying the contents of the capsule and
adding a suitable diluent.
Cont.
3. Lactose is most commonly used diluent
because it is colourless, odourless,
soluble and is generally harmless and
has good flow properties.
4. Some patients may be unable to tolerate
lactose and a suitable inert alternative
diluent, for instance light kaolin, would
then be used.
Powder calculations
• Always calculate for at least 1 extra powder to
compensate loss of powder during
manipulations.
• If amount of active ingredient is less than
minimum weighable quantity than dilutions
(triturations) are to be made.
• Min. weighable quantity is diluted over several
time to obtain requested dose.
While dealing powders calculations
Powder calculations:
A. Doubling up method
B. Calculations involving powder volumes
Example: E.g.
Rx
Hyoscine HBr 300 mcg
mitte 4 powders
one to given 30minutes before journey
(Remember: minimum powder weight for divided
powder = 120mg)
Calculate for 5 doses
Active req. = ?
Diluent (lactose) req. = ?
Powder calculations:
• Step-1
• Hyoscine HBr =100mg
• Diluent =900mg
• Step-2
• Triturate A =100mg
• Diluent =900mg
• Step-3
• Triturate B =?
• Diluent =?
Folding of paper
It involves following steps:
1. The long edge away from the dispenser should be turned over to about one-7th of the paper width.
2. The powder should be weighed accurately and placed on the paper towards the folded edge of the centre of the paper.
3. The unfolded long edge should then be brought over the powder to meet the crease of the folded edge and the flap closed over it.
Folding of paper
4. The folded edge should then be folded over(towards the dispenser)so that it covers about half the powder packet.
5. The short edges of the powder packet should be folded over. using a powder cradle if available, so that flaps are of equal lengths and the folded powder fits neatly into a box a jar. Before making these folds ensure that there is no powder in the ends to be folded, otherwise it may fall out and be lost.
Folding of paper
Advantages of powders:
1. Good chemical stability compared with fluids
2. useful for bulky drugs with large dose, e.g.
indigestion powder.
3. Easy to swallow even in large bulk, especially
if mixed with drink food (useful for stomach-
tube feeding)
4. The smaller particle size of powders causes
more rapid dissolution in body fluids,
increases drug bioavailability, and decreases
gastric irritation compared with tablets.
Advantages of powders:
5. Faster dissolution rate/Bioavailability
6. Rapid onset of action
7. Can be taken orally by some patients
who are unable to swallow other solid
dosage forms such as capsules and
tablets.
Disadvantages of powders:
1. Not suitable for drugs unstable in
atmospheric conditions
2. Not suitable for bitter, nauseating,
deliquescent and corrosive drugs.
3. Inaccuracy of dose in case of bulk
powder
4. Inconvenient to carry.
Shelf life and storage of internal
powders
1. Shelf life of internal powders is 2-4
weeks.
2. Proprietary powders often have a longer
shelf life because of protective
packaging.
3. Storage for these powders should be
moisture proof and airtight.
Shelf life and storage of external
powders
1. Shelf life of external powders is 4
weeks.
2. Dry powders should remain stable for
long period of time if packaged and
protected from atmosphere.
3. Store in a cool and dry place.
Containers for internal powders
• Extemporaneously prepared individually
wrapped powders are often dispensed in a
paperboard box.
• It is preferable to use a screw-top glass or
plastic container which provides an air
tight seal and protection against moisture.
• Bulk powders are packed in an airtight
glass or plastic jar.
Containers for internal powders
Containers for external powders
• Powders for external use may be packed
in glass, metal or plastic containers with a
sifter-type cap. Some are also available
commercially in pressurized containers,
containing other excipients such as
propellant and lubricants.
Containers for external powders
Labels and advice for internal
powders
• Powders are usually mixed with water or
another suitable liquid before taking,
depending upon their solubility.
• Powders for babies can be placed directly
into mouth followed by a drink to wash
down the powder.
• Bulk powders should be shaken and
measured carefully before dissolving in a
little water and taking.
Labels and advice for internal powders:
Labels and advice for external powders
• For external use only.
• Store in cool ,dry place.
Labels and advice for external powders:
Uses of powders:
• Powders are used as counter-irritant e.g
/camphor starch dusting powder.
• Rhubarb powder is used in dyspepsia.
• Chlorhexidine dusting powder is used as
antimicrobial.
• Dover’s powder( ipecacuanha and opium)
is used as antipyretic.
• Magnesium trisilicate powder is used as
antacid and anti-flatulent.
Uses of powders:
• Powders are also used as antiseptics.
Uses of powders:
• Ibuprofen powder is used to treat juvenile
arthritis.
• Rumford is used as aluminium free
baking powder.
Uses of powders:
• Powders are also used in cosmetics as
face powders.
Uses of powders:
• Prickly heat powders are used to relief
skin burn.
Uses of powders:
• Baby powders are used to protect skin
and nappy rashes.
Granules
TOPIC CONTENTS:
Granules: • a)Introduction
• b) Classification
• c)Method of preparation
• d)Advantages and disadvantages
• e)Shelf life and storage
• f)Containers
• g)Packaging
• h)Labeling
• i)Pharmaceutical uses
Introduction
• Granules are powder agglomerated to produce
large free flowing particles.
• Granules are particles ranging in size from
about 4 to 10 mesh.
• They are irregularly shaped but may be
prepared to be spherical.
• Granulation are also used as intermediates in
the preparation of capsule and tablets, since
they flow more smoothly and predictably than
do small powder particles.
Granules
Why we prepare granules when we have
powders?
1. To avoid powder segregation.
2. To enhance the flow of powder.
3. Granules have higher porosity than
powders.
4. To improve the compressibility of
powders.
5. Materials, which are slightly
hygroscope, may adhere & form a cake
if stored as a powder.
Classification
Granules are classified into following
categories:
1. Effervescent granules.
2. Coated granules.
3. Gastro-resistant granules.
4. Modified release granules.
1: Effervescent granules
• Effervescent granules are uncoated
granules generally containing acid
substances and carbonates or hydrogen
carbonates which react rapidly in the
presence of water to release carbon
dioxide.
• They are intended to be dissolved or
dispersed in water before administration.
Effervescent granules
2: Coated granules
• Coated granules are usually multi-dose
preparations consist of granules coated
with one or more layers of mixtures of
various excipients.
• The substances used as coatings are
usually applied as solution or suspension
in conditions in which evaporation of the
vehicle occur.
Coated granules
3: Gastroresistant granules
• These are delayed release granules that
are intended to resist the gastric fluid and
to release the active substance in
intestinal fluid
• These properties are achieved by
covering the granules with the gastro-
resistant material or by other suitable
means.
Gastro-resistant granules
4: Modified release granules
• They are coated or uncoated granules
which contain special excipients or which
are prepared by special procedure are
both , designed to modify the rate , the
place or the time at which the active
substance or substances are released.
• Modified release granules include
prolonged release granules and delayed
release granules.
Modified release granules
Advantages and Disadvantages of granules
Advantages
1. Granules are more flowable compared to powder.
2. Segregation of the constituents of the powder mixture could be avoided by granulation.
3. Granules are more stable against humidity and atmosphere.
4. Granules are more easily wetted by liquids than light and fluffy powders.
Disadvantages
1. The masking of bitter tastes may be a problem with this type of preparation.
2. Granules are not a good method of administering potent drug with low dose.
3. Instability in presence of moisture.
4. Problems in packaging and storage.
Methods of preparation
Granules are generally prepared by two
methods.
1) Wet method
2) Dry method
Wet method:
• 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.
• The granules are placed on drying trays
and are dried by air or under heat.
• The granules are periodically moved
about on the drying trays to prevent
adhesion into a large mass.
Wet method:
• 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.
Fluid bed processing:
Dry method:
Dry granulation is performed by two
ways.
a) Roll compactor
b) Slugging
a) Roll compactor:
• Dry powder is passed through a roll compactor
and then through a granulating machine.
• A roll compactor, also called a roll press or roller
compactor, processes a fine powder into dense
sheets or forms by forcing it through two
mechanically rotating metal rolls running counter
to each other .
• The surface of the compacting rolls may be
smooth or may have pocket indentations or
corrugations that allow compaction of different
forms and textures.
Cont..
• The compacted powder is granulated
to uniform particle size in a
mechanical granulator. Powder
compactors are generally combined
in sequence in integrated compactor–
granulation systems.
a) Roll compactor:
b) Slugging:
• 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.
• The slugs are generally flat-faced and are
about 2.5 cm (1 inch) in diameter.
Cont.
• The slugs are granulated into the desired
particle size, generally for use in the
production of tablets. The dry process
often results in the production of fines,
that is, powder that has not agglomerated
into granules. These fines are separated,
collected, and reprocessed.
Preparation of effervescent granules:
These granules are prepared by two
methods:
A) Fusion method
B) Wet method
A) Fusion 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 sieves and the mixing equipment should
be made of stainless steel or other material
resistant to the effect of the acids.
Cont.
• 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.
• 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.
Cont.
• 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.
B) 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 for granulation.
• In this 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.
Example:
• Sodium citrate and tartrate B.P.
• Ingredients Quantity
1) Sodium bicarbonate 510gm
2) Tartaric acid 270gm
3) Citric acid 180gm
4) Sucrose 150gm
Shelf life and storage:
• Shelf life of granules is 2-3 weeks.
• Granules should be stored in airtight
containers.
• Granules should be placed at cool and dry
place.
Container
• Granules should be kept in air tight container.
Container:
Label and advice
• Dissolve or mix with water before taking.
• A normal dose is 1-5 g of the powder
taken in liquid, when required.
• Antacids are usually taken before meals
and at bedtime.
Label and advice:
pharmaceutical uses:
• Effervescent granules are used as an antacid.
pharmaceutical uses:
• Methylcellulose granules are used as a
laxative.
Uses of granules:
• Granules are also used in fertilizer industry.
Uses of granules:
• Granules are used for instant preparation of
solutions and suspensions.
Uses of granules:
• Lactinex granules are used in uncomplicated
diarrhea.
Uses of granules:
• Granules are also used as animal foods.
9- Relatively simple method of processing/formulation
Powders 1- Comparatively poor flow properties
Granules
1- Flow well compared to tablets, good
2- Has less surface area, more stable to atm. effect
3- Less likely
4- More easily wetted by the solvents, good choice reconstitution liquids
5- Good compressibility
6- Relatively more uniformity of contents in case of granules
7- Generate less dust on handling
8- Have a more elegant appearance
9- It involves more processing, exposure to heat and contact with solvents
2- Relatively less stable (physically and Chemically) due to inc. S.A & Atm. Effect
3- More likely to hardening / cake formation on long storage
4- For some powders, drugs float on the surface, difficult to make solution
5- Relatively poor compressibility
6- Chances of non uniform dosing are more
7- More dust due to small particle size
8- Comparatively less appealing
Powders VS Granules