POWDERS
Powders as a Dosage Form
Powders are prepared either as dusting powders
which are applied locally, dentifrices, products for
reconstitution, insufflations and aerosols.
 Advantages of Powders as a dosage form:
Flexibility in compounding and good chemical stability.
 Disadvantages of powders as a dosage form:
• Time-consuming to prepare
• Not suited well for dispensing the unpleasant-tasting or
hygroscopic drugs.
• Inaccuracy of dose for bulk powders.
The dose is influenced by many factors, including size of
measuring spoon, density of powder, humidity, degree of
settling and fluffiness due to agitation.
Preparation of powder dosage forms
Size reduction
Reduction of particle size of all ingredients with the
same range to prevent separation of large and small
particles.
Trituration
This term refers to the process
of reducing substances to fine
particles by rubbing them in a
mortar with a pestle. This results
in
blending
powders
and
breaking up soft aggregates of
powders.
When
granular
or
crystalline
materials
are
to
be
incorporated into a powdered product, these materials are
triturated individually and then blended together in the
mortar.
Pulverization by Intervention
This is the process of reducing the state of solids with the
additional material as volatile solvents which can be
removed easily after the pulverization has been completed
and the powdered material is obtained.
This technique is applied to substances which are gummy
and tend to reagglomerate or which resist grinding.
Example:
Camphor which cannot be pulverized easily by
trituration because of its gummy properties, can be
reduced to a fine powder by the addition of a small
amount of alcohol or other volatile solvent.
Iodine crystals can be triturated with the aid of a small
quantity of ether.


Levigation
In this process a paste is first formed by the addition of a
suitable non-solvent to the solid material.
Particle-size reduction then is accomplished by robbing the
paste in a mortar with a pestle.
Levigation technique is used to incorporate solids into
ointments and suspensions.
Blending (Mixing)
Blending is used when two or more substances are to be
combined to form a uniform powder mixture.
Depending upon the nature of the ingredients and the
amount of powder to be prepared mixing may be by
spatulation, trituration, sifting, tumbling or by mechanical
mixers.
Spatulation
This method is used when small amounts of powders are to
be blended by the movement of a spatula through the
powders on a sheet of paper or an ointment slab.
Trituration
The method may be employed
both to reduce and mix powders.
Porcelain or Wedgewood mortar is
used.
For chemicals that may stain the
porcelain or Wedgewood surface,
a glass mortar may be preferred.
When potent substances are to be mixed with a large
amount of diluent, geometric dilution method is employed
to ensure the uniform distribution of the potent drug.
By this method, the potent drug placed upon an equal volume the diluent
in a mortar and the mixture is mixed by trituration. Then a second
portion of diluent equal in volume to the powder mixture in the mortar is
added, and the trituration is repeated. This process is continued by
adding equal volumes of diluent to that powder present in the mortar
and repeating the mixing until all of the diluent is incorporated.
Sifting
Powders may also be mixed by passing them through
sifters.
This process results in a light fluffy product.
This process is not acceptable
for
the
incorporation
of
potent drugs into a diluent base.
Tumbling
The powder enclosed in a large container which rotates
generally by a motorized process.
Such blenders are widely employed in industry to blend
large amounts of powder.
Problems in powder manufacture
The
incorporation
of
volatile
substances, eutectic mixtures, liquids
and
hygroscopic
powders
presents
substances
into
problems
that
require special treatments.
Volatile Substances
The loss of camphor, menthol and essential
oils by volatilization when incorporated into
powders may be prevented or retarded by use
of heat-sealed plastic bags or by double
wrapping with a waxed or glassine paper
inside a bond paper.
Eutectic Mixtures
Liquids result from the combination of
phenol,
camphor,
antipyrne,
menthol,
phenacetin,
thymol,
acetanilid,
aspirin, salol at ordinary temperatures.
These eutectic mixtures can be incorporated into
powders by addition of an inert diluent or absorbent.
kaolin, starch, bentonite are used as absorbents
Incorporation of 20% silicic acid (particle size, 50 µm)
prevented eutexia with aspirin, phenyl salicylate.
This technique offers the advantage of extended
product stability.
Magnesium
carbonate or light magnesium oxide are
used commonly as effective diluents for this purpose. An
amount of diluent equal to the eutectic compounds is
sufficient to prevent liquefaction for about 2 weeks.
Each eutectic compound should be mixed first with a
portion of the diluent and gently blended together,
preferably with a spatula on a sheet of paper.
Liquids
Liquids may be incorporated into divided powders.
Magnesium carbonate, starch or lactose may be added
to increase the absorbability of the powders if necessary.
When the liquid is a solvent for a nonvolatile heat-stable
compound, it may be evaporated gently on a water bath.
Lactose may be added during the evaporation to increase
the rate of solvent loss by increasing the surface area.
Some extracts and tinctures may be treated in this manner,
although the use of an equivalent amount of a powdered
extract is a more desirable technique.
Hygroscopic Substances
Substances that become moist because of affinity for
moisture in the air may be prepared as divided powders
by adding inert diluents.
Double-wrapping is desirable for further protection.
Extremely Hygroscopic compounds cannot be prepared
as powders.
Use and Packaging of Powders
Depending upon their use, powders are
packaged and dispensed in two main ways:
Bulk powders.
Divided powders.
BULK POWDERS
Example of the bulk powders are:
Oral powders: as antacid and laxative powders, it can
be taken by mixing an amount of powder in a portion
of water or other beverage and swallowing as solution
or suspension.
Douche
powders: generally dissolved in warm water
and used as antiseptics or cleansing agents for a body
cavity as for vaginal use.
Douche powders are Dispensed in wide-mouth glass
jars serves to protect against air and moisture or loss
of volatile materials
 Dusting
Powders: Medicated or non-
medicated for external application for
various parts of the body as lubricants,
protectives, absorbents, antiseptics,
astringents and antiperspirants agents.
• Dusting Powders are usually dispensed in sifter
•
containers for convenient application to the skin.
Foot powders and talc powders are currently available
as aerosols.
Dentifrices: Dental cleansing powders, used in dental
hygiene.
Denture powders, some used as dentifrices and others
as adhesives to hold the dentures in place.
All powders should be stored in tightly closed containers
for Protection against humidity, air oxidation and loss of
volatile ingredients.
Dispensing powdered drugs in bulk amounts limited to
non-potent substances.
Powders containing potent substances or those that
should be administered in controlled dosage are
Supplied to the patient in divided amounts.
divided POWDERS
 After the powder has been mixed, it may
be divided into individual doses.
 Each divided portion of powder may be placed on a
small piece of paper or metal foil which is then folded or
in small heat-sealed plastic bags so as to enclose the
medication.
 Hygroscopic and volatile drugs can
be protected by using a waxed paper;
Pharmaceutical powders may be classified as free-flowing
or cohesive (non-free-flowing).
Flow properties are significantly affected by changes in
particle size, density, shape, electrostatic charge, and
adsorbed moisture, which may arise from processing or
formulation.
Preformulation, powder flow should be determined for
the improvement of pharmaceutical formulation and
consequences of processing.
This subject becomes vital for the development of a
commercial solid dosage form containing a large
percentage of cohesive material.
Factors affecting Powder Flowability:
1-
Particle size:
Frictional and
cohesive forces (resistance to flow) are
increased
as
the
particle
size
is
reduced .
Very fine particles do not flow as large particles.
In general, particles in the size range of 250-2000 µ flow
freely if the shape is agreeable. Particles in the size
range of 75-250 µ may flow freely or cause problems,
depending on shape and other factors. With particles less
than 100 µ in size, flow is a problem.
2-
Density
and
porosity:
-
Particles with high density and low
porosity tend to posses free flowing
properties.
3-
Particle shape:
particles
presents
contact
than
Rough irregular
more
smooth
points
of
spherical
particles thus Spherical particles flow
4- better
Particle
size distribution: Larger amount of
than needles.
fines can inhibit poor flowing.
5- Moisture
content:
the cohesiveness.
Drying the powders will reduce
Flow rate determination
• Powder flows through an orifice onto
an electronic balance.
• Flow rate is determined by measuring weight of powder
pass through an orifice per time (g/sec).
• Several flow rate determinations through a variety of
orifice sizes (1/8 to 1/2 inches) should be made.
• In general, the greater the standard deviation between
multiple flow rate measurements, the greater is the
weight variation in products produced from that powder.
Particle Size Analysis
The particles of pharmaceutical powders may be coarse to
extremely fine.
The USP utilizes terms which are
related to the proportion of powder
that is capable of passing through
the openings of standardized sieves
of varying dimensions in a specified
time.
Standard Sieve Shaker
Opening of Standard Sieves
Sieve Number
2
3.5
4
8
10
20
30
40
50
60
70
80
100
120
200
230
270
325
400
Sieve Opening
9.5 mm
5.6 mm
4.75 mm
2.36 mm
2.00 mm
850 µm
600 µm
425 µm
300 µm
250 µm
212 µm
180 µm
150 µm
125 µm
75 µm
63 µm
53 µm
45 µm
38 µm
Sieve Analysis
Coarse powder -All particles pass through
No. 20 sieve and not more 60% through No. 40 sieve.
Moderately Coarse powder -All particles pass through No.
40 sieve an not more than 60% through No. 60 sieve
Fine powder -All particles pass through No. 80 sieve.
There is no limit as to greater fineness.
Very Fine powder -All particles pass through No. 120
sieve. There is no limit as to greater fineness.
Methods for the determination of particle size:
Methods of particle size determinations include techniques
that provide average particle size by:
Weight (sieve method, light scattering, sedimentation
method).
Volume (light scattering, electronic sensing zone, light
obstruction, air permeation and the optical
microscope).
Sieving: In which particles are
passed
by
mechanical
shaking
through a series of sieves of known
and successively smaller size and
the determination of the proportion
of powder passing through or being
held on each sieve (range: from
about 50 to 3360 micrometers,
depending upon sieve sizes).
Sieve Analysis
Microscopy: In which the particles are sized through
the use of a calibrated network background (range:
0.2 to 100 micrometers)
Sedimentation :
Particle size is determined by measuring the
settling velocity of particles through a liquid
medium in a gravitational or centrifugal environment.
Sedimentation rate may be calculated from Stokes' law
Using the "Andreasen Pipet.“
The Andreasen pipet is designed where a sample can be
removed from the lower portion at selected time intervals.
The powder is dispersed in a nonsolvent in the Andreasen
Pipet.
Agitated, and 20 mL samples removed over a period of
time.
Each 20 mL sample is dried and weighed.
Light energy diffraction:
Particle size is determined by the reduction in light reaching
the sensor when the particles, dispersed in a liquid or gas,
passes through the sensing zone.
Laser holography:
in which a pulsed laser is fired
through an aerosolized particle spray
and
photographed
dimensions
camera,
with
a
in
three
holographic
Angles of Repose Ф
The angle of repose is a relatively simple technique
for estimating the flowability of a powder.
Such measurements give at least a qualitative
assessment of the internal cohesive and frictional
effects under low levels of external loading, as might
apply in powder mixing, or in tablet die or capsule
shell filling operations.
The
angle
of
repose
can
be
determined experimentally by allowing
a powder to flow through a funnel and
fall freely onto a surface.
The height and diameter of the resulting cone is measured.
It is the maximum angle that can be obtained between the free
standing surface of a powder heap and the horizontal plane.
Angle of repose Ф can be defined by the equation:
Tan Ф =
Where:
2h
D
h is the height of the powder cone.
D is the diameter of the powder cone.
 Values of Ф between 20° - 40° indicate reasonable flow.
 Powders with low angles of repose will flow freely
 Above 50° the powder flows only with great difficulty.
Mass-Volume Relationships
The mass of a bulk powder can be accuracy determined
but measurement of the volume is more complicated.
The main problem arises in measuring the volume of
bulk powders is the presence of three types of air
spaces or voids between particles.
1.Open intraparticulate voids:-
Those within a single particle but open to the external
environment.
2. Closed intraparticulate voids:-
Those within a single particle but closed to the external
environment.
3. Interparticulate voids:-
The air spaces between individual particles.
Therefore, at least three interpretations of "powder
volume may be proposed
The true volume (Vt):
The total volume of the solid particles, which excludes all
spaces greater than molecular dimensions, and which has
a characteristic value for each material.
The granular volume (particle volume) (Vg):
The cumulative volume occupied by the particles,
including all intraparticulate (but not interparticulate)
voids.
The bulk volume (Vbulk):
The total volume occupied by the entire powder mass
under the particular packing achieved during the meas
POROSITY, VOID AND BULK VOLUME
Packing and flow of powders are important for:
 Impacting the size of container required for packaging
 The flow of granulations
 The efficiency of the filling apparatus during the tabletting
 Encapsulating process.
A number of characteristics can be used to describe
powders including:
Porosity, true volume, bulk volume, apparent density, true
density, and bulkiness.
The void is the space between the particles which resulting
in a porosity.
If particles are not uniform, the smaller particles will slip
into the void spaces between the larger particles and
decrease the void areas.
The Void =
Where:
Bulk Volume, V bulk
= The volume occupied by a selected
weight of a powder.
The True volume, Vt = The space occupied by the powder
exclusive of spaces greater than
the intramolecular space.
The Porosity =
X 100
The bulk volume = True volume + Porosity
APPARENT DENSITY, TRUE DENSITY AND
BULKINESS
Bulk density is of great importance for capsule filling,
tablet Compressibility and for the homogeneity of
formulation in which there are large differences in drug
and excipient densities.
Apparent bulk density (g/ml) is determined by pouring
presieved (40-mesh) bulk drug into a graduated cylinder
via a large funnel and measuring the volume and weight
"as is."
Powders with low apparent density and large bulk volume
are "light" powders, and those with high apparent density
and small bulk volume are "heavy" powders.
The Apparent Density Pa=
The True Density P =
Weight
Weight
of
theSample
Vbulk
of
theSample
V
The bulkiness, B = is the reciprocal
of the apparent density
B = 1 /pa
Tapped density is determined by placing a graduated
cylinder containing a known mass of drug or formulation on
a mechanical tapper apparatus, which is operated for a
fixed number of taps (≈1000) until the powder bed volume
has reached a minimum.
Using the weight of drug in the
cylinder
and
this
minimum
volume, tapped density can be
determined.
Compressibility
% Compressibility =
 Pt  Po 


 Pt 
Where:
Pt = The tapped bulk density
P0 = The initial bulk density
X 100
A simple indication of the flow property of a powder is
given by using of compressibility index (I)
Compressibility index (I) =
 V 
1

 V 0 

X 100
Where:
V = the volume occupied by a sample of the powder after
tapping procedure
Vo = the volume before tapping.
Values of I below 15% usually give rise to good flow
characteristics, but above 25% indicate poor flowability.