University of Kerbala

College of Pharmacy

Pharmaceutical Technology II
Powdered Dosage Forms

Jinan M. AL-Mousawy
Lecturer in Pharmaceutics
 Powders
Powders are mixtures of dry,
finely divided drugs and/or
excipients intended for
internal or external use.
Powders are the basis of
many other solid dosage
forms such as tablets,
capsules, granules,etc.
 Uses of Powders
Used as medication
itself

Used In the Preparation of other dosage forms

Semisolids
Solid dosage forms liquid dosage forms (e.g. ointments
(e.g. tablets and capsules) (e.g. solutions and suspensions) and creams)
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 Advantages of powders
1. Simple: The simplest one.
2. Used both internally and externally.
3. Good chemical stability compared with fluids.
4. Easy to carry than the liquid dosage forms.
5. Solid dosage forms are more chemically stable than liquid ones. The
shelf life of powders for antibiotic suspension is 2-3 years, but once they
are reconstituted with water it is only 1-2 weeks.
6. Powders and granules are a convenient form in which to dispense drugs
with a high dose. For example, the dose of Compound Magnesium
Trisilicate Oral Powder is 1-5 g and, although it is feasible to manufacture
tablets to supply this dose, it is often more acceptable to the patients to
disperse a powder in water and swallow it as a draught.
7. Orally administered powders and granules of soluble medicaments have
a faster dissolution rate than tablets or capsules, as these must first
disintegrate before the drug dissolves. Drug release from such powdered
or granulated preparations will therefore generally be faster than from
the corresponding tablet or capsule.
 Disadvantages
1. Difficult to dispense hygroscopic drugs.
2. Can not dispense volatile drugs.
3. Agglomeration can occur especially in fine powders in which
particles adhere to each other to form clusters (which may
cause segregation).
4. The bitter taste of some drugs is a well-known formulation
problem. Several formulation strategies to mask the bitter
taste of these drugs include the sugar coating process by
sweeteners like sugars or polymer coating and the
formulation into an effervescent drug product. The evolution
of CO2 during effervescence reaction causes numbness of
taste buds in the tongue leading to masking the bitter taste
of drugs.
5. Powders and granules are not the formulation strategy for the
drugs which are inactivated in, or cause damage to the stomach.
These drugs, like erythromycin, must be formulated as enteric-
coated granules or tablets instead of powders or normal granules.

6. Bulk powders or bulk granules are not suitable for the

administration of potent drugs with a low dose like digoxin. This is
because individual doses are extracted from the bulk using 5ml
spoon. This method is subject to such variables as variation in
spoon fill (e.g. ‘level’ and ‘heaped’ spoonfuls) and variations in the
bulk density of different batches of a powder. Divided dosage form
preparations and tablets or capsules are the best dosage forms of
these drugs. But tablets and capsules are used commonly for this
purpose.

7. It is less convenient for patients to carry a large container

containing several doses compared to a small container or strips
containing unit doses.
Characterization of powders
•Before their use in the preparation of pharmaceutical
products, solid materials first are characterized to determine
their chemical and physical features, including
1.morphology,
2.purity,
3.solubility,
4.flowability,
5.stability,
6.particle size,
7.uniformity, and
8.compatibility with any other formulation components
Particle size
•The adjustment and control of a drug and other materials
powder's particle size; enable both the efficient production of a
finished dosage form and the optimum therapeutic efficacy.
•United States Pharmacopeia (USP) uses these terms: very coarse,
coarse, moderately coarse, fine, and very fine, 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
•Sieves can be referred to either by their aperture size or by their
mesh size (or sieve number).
•The mesh size is the number of wires per linear inch

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Particle size can influence a variety of important
factors
1.Dissolution rate of particles intended to dissolve; drug
micronization can increase the rate of drug dissolution and
its bioavailability
2.Suspendability of particles intended to remain un-dissolved
but uniformly dispersed in a liquid vehicle (e.g., fine
dispersions have particles approximately 0.5 to 10 μm)
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
 Important applications of Particle Size
•The surface area affects the effectiveness
of compounds.
Example: The particle size reduction of
griseofulvin led to a dose half that of the
marketed product. Also, it affects on the
onset of action.
•Injectable suspensions, e.g., procaine
penicillin are greatly affected by the
particle size (bioavailability, syringe-ability
pain).
Micromeritics
Micromeritics is the science of small particles; a particle is any
unit of matter having defined physical dimensions .
Micromeritics is the study of a number of characteristics,
including:
• particle size and
•size distribution,
•shape,
•angle of repose,
•porosity,
•true volume,
•bulk volume,
•apparent density, and
•bulkiness
Particles Size Measurement
1-Microscope
•The BP recommends that at least
625 particles should be counted.
•If the particle size distribution is
wide, it may be necessary to
count more particles.
•If the particle size distribution is
narrow, as few as 200 particles
may be sufficient.
2- SIEVING
It is the most widely used
method for measuring
particle size distribution
because it is inexpensive,
simple & rapid with little
variation between
operators.
 Disadvantages of Sieving

– Sieving errors can arise from a number of variables

including:
• Duration of agitation
• Intensity of agitation.
– Need large volumes of samples
– Very small particle size (< 5 μm) can not be
measured.

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3- SEDIMENTATION
The sedimentation method is
based on the dependence of
rate of sedimentation of the
particles on their size as
expressed by stokes law.
This method can be used for particle size measurements
in the range of 1μm to 200μm.
We notice that when a particle falls into a liquid, it slowly
settles down. The bigger and denser it settles fast. The
smaller and lighter, settles slowly. This principle is used
in particle size determination. Since in a given powder,
all the particles are of same density, they settle only
based on size. So large particles settle fast and at the
bottom of the sediment. Similarly smaller ones settle
slower and lie at the top of sediment.
The size of particles here is expressed as stokes diameter
dst.

This represents the diameter of an equivalent sphere

which has the same rate of sedimentation.
Methods: There are different methods to carry out this
procedure like anderson pipette method, balance
method and hydrometer method.

Here the particles are suspended in a liquid medium and

allowed to sediment or settle down in a cylindrical
tube. The rate of sedimentation varies based on the
particle size. Hence different layers of sediment are
formed. These different layer are taken as particles of
particular size are only present in the sediment layer.
The weight of the sediment layer is measured. This
gives the weight of particles of particular size in the
entire sample.
Advantages: Reliable as whole of sample is screened. But
is a rough estimate of size in each layer.
New Methods
•Light diffraction
•Laser technology
•Coulter Counter
•Electron Microscope
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Particle Size Reduction
Particle size reduction
is called trituration,
comminution, grinding
and milling.
Trituration
• On a small scale, the pharmacist reduces
the size of powders by grinding with a
mortar and pestle (trituration).
• A finer particle size is accomplished by
using a mortar with a rough surface
(porcelain mortar).
Hammer mill
Hammer mill is large scale mill that
uses a high speed rotor to which a
number of hammers are fixed.
The material is retained until it is
small enough to fall through the
screen in the milling chamber.
Mixing of powders
• Spatulation
•Trituration
• Sifting
• Tumbling
 Spatulation
• It is mixing of small amounts of
powders by movement of a spatula
through them on a sheet of paper.
• It is not suitable for large quantities
of powders or for powders
containing potent substances,
because homogeneous blending is
not ensured.
• Trituration may be
employed both to traturate
and to mix powders. If
simple mixing is desired
without communition, 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 is used.
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 Geometric dilution
+ equal amount

A B

A
Potent drug B + equal amount
Diluent
A+B B

+ equal amount

A+B
B
The process is repeated until all of the diluent
B is incorporated
 Sifting (sieving)
Powders may also
be mixed by
passing them
through sifters.
This process is not
acceptable for
mixing of potent
drugs with a
diluent.
 Tumbling
• Another method of mixing powders is tumbling the
powder in a rotating chamber.
• Mixing by this process is thorough but time consuming.
Special small-scale and large-scale motorized powder
blenders are widely used in industry.

Laboratory-scale V-
Industrial-size solid-state
blender
processor or twin shell blender
Powder Characterization
2-ANGLE OF REPOSE
•The angle of repose is a simple technique
for estimating the flow properties of a
powder.
•It can be determined by allowing a
powder to flow through a funnel and fall
onto a surface.
•The height and diameter of the cone are
measured and the angle of repose is:
tan q = h/r
 •Powders with a low angle of repose
flow easily, and powders with a high
angle of repose flow poorly.
•A number of factors, including shape
and size, determine the flow properties
of powders.
•Spherical particles flow better than
needles.
•Very fine particles do not flow as freely
as large particles.
 Classification of powders or granules
according to its route of administration:
1. Oral powders
2. Inhalation powders
3. Nasal powders
4. Topical powders
5. Dusting powders
6. Ear powders
7. Oral powders or granules for solution or
suspension
8. Oral powders or granules for syrup
9. Powders for injection
1. Oral powders
• Oral powders are formulations composed of
solid, loose, dry particles of varying degrees of
fine particle size. They contain one or more
active substances with or without excipients
and if necessary, approved coloring matter
and flavoring.
• They are generally administered in or with
water or another suitable liquid, or they may
also be swallowed directly
2. Inhalation powders
• The powders for inhalation are considered the most
effective methods of delivering active ingredients to
the lung for the treatment of asthma and chronic
obstructive pulmonary disease.
• It needs an inhalation device used by the patient at the
time of administration where the drug is inhaled as a
cloud of fine particles. The drug may be preloaded
in the inhalation device or filled into hard gelatin
capsules or foil blisters which are loaded into an
inhalation device prior to use
• The suitable particle size to achieve the best
delivery to the lung is preferably less than
5μm (micronized).
• The high-energy powders produced by
micronization have poor flow properties
because of their static, cohesive and adhesive
nature.
• To improve the flow properties, poor flowing
drug particles are generally mixed with larger
‘carrier’ particles (median size usually 30-150
μm) of an inert excipient, usually lactose
(lactose monohydrate).
3. Nasal powders
• Nasal powders have medicinal effects
intended for inhalation into the nasal cavity by
means of a suitable device.
• Some potent drugs are presented in this way
because they are rapidly absorbed when
administered as a fine powder via the nose.
• Also, the drug is mixed with an inert excipient
such as lactose that liberates the drug at the
administration time.
4. Topical powders
• They are used for cutaneous application.
• They are solid, loose, dry particles of varying
degrees of fineness that contain one or more
active pharmaceutical ingredients, with or
without excipients, and if necessary, appropriate
coloring matter.
• Sterile powders for cutaneous application must
be formulated using materials and methods that
ensure sterility and to avoid the introduction of
contaminants and the growth of micro-
organisms.
 5. Dusting powders
• Dusting powders are powders for cutaneous
application which have a suitable fineness.
• Dusting powders are normally dispensed in glass or
metal containers with a perforated lid. So, the powder
must flow well from such container to ensure that it
can be dusted over the affected area.
• The active ingredients must therefore be diluted with
materials having reasonably good flow properties such
as purified talc or maize starch. Canesten Powder
(clotrimazole) is used as an antifungal agent.
• They may be used for lubricant purposes such as Talc
Dusting Powder.
 dispensing of Powders
1) Divided powders e.g., sachets

2) Undivided (Bulk) powders

a.dusting powder
b.effervescent powder
 Bulk Powders
Antacids is an example of bulk powders in
which the patient takes the dose himself by
mixing with water.
Granules
Problems of powder formulation
1- Efflorescent powders
Crystalline substances which loose their water
of crystallization during storage.

The liberated water convert the powder to a

paste and finally, it becomes stone-like upon
drying. Ex: citric acid, caffeine, ferrous sulfate,
Cocaine, codeine
Solutions:
• The first strategy is to store these powders in a tight container, in
order to limit the amount of air flow through the container, and
thereby reduce the release of moisture. Secondly, when possible,
substitute the drug with its anhydrous form. In other words, use the
same drug in powder form, but a form of the drug that does not
contain any water of hydration.
• Convert the powder into granules to decrease the surface area, thus
decrease the contact with environment.
Hygroscopic and deliquescent powder
• Hygroscopic powders are powders that can
absorb moisture from the air and tend to get
damp and clumpy. Deliquescent powders
absorb so much moisture from the air, they
can actually solubilize themselves and
transform from a powder into a solution.
Therefore, we must prevent this from
occurring in our formulation .
ex:
 solutions
• first strategy is the same as for efflorescent
powders, namely to store these powders in a
tight container, preferably in an area of low
humidity to limit access to moisture from the
air. The second strategy would be to add an
inert powder that would preferentially absorb
any water or moisture from the air like lactose
,light magnesium oxide.
Eutectic Mixtures
They are mixture of substances that liquefy when mixed
together. The melting points of many eutectic mixtures are
below room temperature.

Ex: phenol, menthol, camphor, aspirin ,acetaminophen and

benzocaine.
Solution:

1. Separate the eutectic mixture by formulating

one of them as powder and the second as
granules to decrease the contact between
them.
2. Using adsorbent material such as kaolin to
decrease contact of the powder