Powders
A pharmaceutical powder is a mixture of finely
divided drugs and/or chemicals in dry form
meant for internal or external use. This should
differentiated from general use of term
powder or powdered which is commonly used
to describe the physical state of a single
chemical substance or single drug.
A powder may be finely subdivided
preparation, coarsely comminuted product or
product of intermediate particle size. It may be
prepared from a naturally occurring dried
vegetable drug or it may be a physical
admixture of two or more powdered pure
chemical agents..
Powders may contain small proportion of
liquid dispersed thoroughly and uniformly
over the solid components of the mixture or
powder may be composed entirely of the
solid materials.
According to BP the particle size range is 1.2 –
1.7 mm.
Excipients may be added as coloring, flavoring
or sweetening agents.
Powders may contain small proportion of
liquid dispersed uniformly over the solid
particles.
Granules which are used as a dosage form
consist of powder particles aggregated to form
large particles of size range 2 – 4 mm.
Advantages of powders
1. Flexibility of compounding
2- More stable than liquid preparation ( good
chemical stability)
3- Convenient to dispense drugs with large doses
such as compound magnesium trisilicate oral
powder.
4- Rapid dispersion of ingredients because of
the small particle size.
5- Orally administered powders and granules
of soluble drugs have a faster dissolution
rate and absorption than tablets and
capsules.
Disadvantages of powders
1. Time consuming in preparation especially
in divided doses
2. Dose inaccuracy
3. Unsuitability for many unpleasant tasting
drugs
4- They are not suitable dosage form for
potent drugs
5- Powders and granules are not suitable
dosage forms for drugs which are inactivated
in the stomach
6- Powders containing hygroscopic
aromatic ingredients cannot be protected
or
Fundamental properties of powders
Particle size and size distribution
The size of a shape is readily expressed in
terms of its diameter. As the degree of
asymmetry of particles increases, the difficulty
of expressing size in terms of diameter
increases.
Under these conditions, there is no one
diameter for a particle. Therefore, we use
equivalent spherical diameter which relates the
size of the particle to the diameter of sphere
having the same surface area (ds), volume (dv)
or sedimentation rate (dst).
1. Surface diameter: (ds)
It is the diameter of sphere having the
same surface area as the particle in
question.
1. Volume diameter: (dv)
The diameter of a sphere having the same
volume as the particle in question.
1. Stoke's diameter: (dst)
It describes the diameter of sphere having
the same sedimentation rate as the
particle in question.
Surface area of spherical particle = π d2
Surface area of asymmetric particle= π d2s
Where ds is the equivalent surface diameter.
Volume of spherical particle = π d3/6
 volume of asymmetric particle = π dv3/6 where
dv is equivalent volume diameter
Specific surface: it is the surface area per unit
volume ( Sv ) or per unit weight (Sw )
Sv = surface area of the particle /
volume of the particle
Sw = surface area of the particle /
weight of the particle
Importance of controlling particle size in
pharmacy
1. The particle size and the surface area of a
drug can affect its physical, chemical, and
pharmacological properties.
2. The particle size of a drug can also affect its
release rate from dosage form.
3- Successful formulation of suspensions
depends on the particle size of the drug.
4- In tablet and capsule manufacture, control
of the particle size is essential for the flow
properties and proper mixing of granules and
powders.
Particle size distribution
Any collection of particles is usually
heterogeneous, i.e. particles of more than one size
are present.
The size ranges present in a sample, and the
number or weight of particles in each size range is
called the particle size distribution, which can be
represented by two curves, the frequency
distribution curve and cumulative frequency
distribution curve.
3- Presentation of the data:A- Table form
Size range
(µm)
0-5
5-10
10-15
Mean
(µm)
2.5
7.5
12.5
No. of particles
96
105
116
% of
particles
Cumulative %
6.5%
6.5
13.6 (6.5+7.1)
21.4
(13.6+7.8)
7.1%
7.8%
15-20
20-25
17.5
22.5
129
150
25-30
27.5
212
30-35
32.5
148
35-40
37.5
127
40-45
42.5
114
45-50
47.5
101
50-55
52.5
92
55-66
57.5
88
8.7%
30.2%
6.8%
5.6%
99.4%
Total = 1478
∑ ni
The cumulative % over size is interpreted as the percent of the number of particles that
are more than the stated size.
e.g. in the table, 99.4% all the particles are more than 57.5 µm.
Frequency -distribution curve
Frequency- distribution curve
Symetric distribution curve
Normal distribution curve
Asymetric distribution curve
Skewed-distribution curve
Cumulative -distribution curve
2-Particle shape and surface area
The shape of the particle has an important
influence on certain properties such as:
A-Flowability: spherical particles are more
flowable than irregular ones
B-Packing properties: irregular particles may be
able to pack together more closely than spherical
particles giving a higher bulk density.
C-Surface area: spherical particles have
minimum surface area per unit volume.
D-Rheological properties:
Pharmaceutical suspensions are also affected
by the shape of the particles that they contain.
•The surface area of the particles affect both
their physical (dissolution rate and adsorption)
and chemical properties
( reaction rate and stability).
Methods of determining particle size
1- Microscopy
The ordinary optical microscope is used for
particle size measurement in the range of 0.5 –
100µ, while the electron microscope is
applicable for sizes ranging from 0.005 – 1.0µ.
A sample of the powder is suspended in a
suitable diluents, mounted on a slide and
placed on a mechanical stage. The
eyepiece is fitted with a micrometer by
which the size of the particle can be
estimated.
Disadvantages of microscopic method
1. The diameter is obtained from only two
dimensions of the particle, length and
width. No estimation of the depth (
thickness) of the particle can be made.
2. A large number of the particles must be
measured (300 – 500) in order to obtain a
good estimation and this renders the
method slow.
Sieving
Powders with particle size range of 50 – 500
µ can be measured by sieving method. This
method utilizes a series of standard sieves
with different mesh sizes.
The sieves are arranged in a nest of about
five sieves with coarsest at the top.
A carefully weighed sample of the powder is
placed on the top sieve and the sieves are
shaken for a certain period of time by the use of
mechanical shaker.
The fraction of powder retained on each sieve
is weighed and a plot of weight against size is
made to obtain the frequency distribution
curve.
Sieving errors can arise from:
Sieving errors can arise from:
A.Overloading of the sieve
A.Forcing the powder through the sieve by
spatula
A.Insufficient time of agitation
A.Inadequate intensity of agitation
3-Sedimentation
The size of particles suspended in a liquid
may be determined by measuring the rate at
which the particles settle down in a
graduated cylinder and applying
Stock's law which states that:
V = h/t = dst2 (p – po) g / 18η
Where:
V = rate of settling.
h= distance of fall in time t
dst = mean particle diameter based on rate of
settling ( stock's diameter)
p = density of the particle
Po = density of the dispersion medium
G = acceleration due to gravity
η=viscosity of the dispersion medium
the diameter obtained by the sedimentation
method is the diameter of sphere having same
sedimentation rate as the particle under test
(Stock's diameter).
Sedimentation method is used for particle
size range of 0.5 - 100µ
For accurate results, two precautions should
be considered:
A.Dilute suspension should be used ( less than
2%) to allow free settling of the particles
without hindrance.
B.A suitable deflocculating agent must be added
to keep the particles separate without
aggregation.
• Several method based on sedimentation are
used, the most important are the pipette
method and the balance method.
The pipette method
An apparatus called Andreasen apparatus is
used. It consists of 500ml vessel containing a 10 ml
pipette which is lower end is 20 cm below the 500
ml mark of the vessel.
500ml of 1% suspension of the powder in the
medium containing suitable deflocculating
agent is introduced into the vessel which is
then shaken to distribute the particles
uniformly throughout the suspension.
At various time intervals, 10 ml samples are
withdrawn and weight of powder present in
each sample is determined either by
evaporating the liquid and weighing the residue,
or by any other suitable assay method.
The particle diameter corresponding to the
various time intervals is calculated from Stock's
law, with h = 20 cm
The balance method
The powder suspension is introduced into a
vessel containing a balance pan at its bottom.
The weight of particles that settle on the
balance pan continuously recorded at various
time intervals, and the particle diameter
corresponding to each weight is calculated from
stock's law, where h= height of suspension
above the balance pan.
Particle volume measurement
An instrument that measure the volume of
particles called coulter counter
This instrument operates on the principle
that when a particle suspended in a conducting
liquid passes through a small orifice, on either
side of which are electrodes, a change in
electric resistance between the electrodes
occurs.
•A constant voltage is applied across the two
electrodes to produce a current
•A dilute suspension of the particles is made
up in a suitable electrolyte solution e.g.
sodium chloride, and then pumped through
the orifice.
•Provided the suspension is sufficiently
dilute, the particles pass through the
orifice one at a time
•As the particles travels through the
orifice, it displace its own volume of
electrolyte resulting in an increase
resistance between the two electrodes
•Such change in resistance produce voltage
pulses which are proportional to the particle
volume and can be amplified, measured and
counted.
•The particle volume can be converted to
particle diameter from the relation:
Volume of spherical particle = π d3/6
Volume of asymmetric particle = π dv3/6
•Coulter counter can be used for measuring
particle size in the range 1- 100µ
Advantages:
1. This equipment can count large number of
particles (500/min) very rapidly.
2. Yield highly reproducible results.
3. Because of the large number of particles,
statistics will be easy and yield high level
of confidence in the distribution of a
sample.
Disadvantages:
1. Cost of equipment.
2. The possibility of orifice blockage by the
particles.
3. The electrolyte used must be specific and
in which the material to be counted is
insoluble.
4. Wrong results are produced if there is
electrolytic back ground.
Powder’s chracters which measured:
1-Porosity
Suppose a powder is placed in a graduated
cylinder, the volume occupied by the powder is
known as the bulk volume (Vb).
The bulk volume of the powder consists of the
true volume of the solid particles (Vp) plus the
volume of the spaces between the particles which
is known as the void volume (V)
Thus
V = Vb - Vp
Thus the porosity or voids ( Ɛ ) of the
powder is defined as " the ratio of the void
volume to the bulk volume".
Thus
Ɛ = V b - Vp / Vb
The porosity is frequently expressed in
percent, Ɛ × 100
2- Density
•Density is defined as the weight per unit
volume.
•There are three types of densities:
1-True density: it is the density of the actual solid
material.
2-Granule density: it is the density of the
material with its intra – particle pores.
3- Bulk density: it is the density of the material
with its intra – particle pores and voids spaces.
3-Cohesion
Cohesion is defined as the stress necessary to
shear a bed of the powder under conditions of
zero normal load.
Factors influencing cohesion:
1-Particle size: fine particles are more cohesive
than coarser ones. Below 10µ, most powders are
extremely cohesive.
Particle density: light particles are more cohesive
than heavy ones.
Particle shape: spherical particles are less
cohesive than irregular ones.
Humidity: a low % of the adsorbed moisture
on the surface of the particles will reduce the
surface energy of the particles and decrease
cohesion of the powder. However, a
continuous film of moisture surrounding the
particles can cause a great increase in
cohesion.
4- Flowability
The ability of a powder to flow is one of
the factors involved in mixing of different
materials to form a powder blend.
The friction forces in a powder can be
measured by angle of repose (ɸ).
The angle of repose (ɸ):
•If the powder is poured freely onto a plane
surface, it forms a cone that has a constant
angle between the surface of the pile and the
horizontal plane. This angle is known as the
angle of repose, and for most pharmaceutical
powders, it ranges from 34 to 48º.
ɸ =h/r
•Where h= height,
r= radius
•The angle of repose depends on the mutual
friction between the particles. With an
increase in friction, the resistance to flown is
increased with subsequent increase in the
angle of repose. The angle of repose permits
evaluation of the granulation before
compression is attempted.
•To improve the flow properties, materials
termed glidants are frequently added to granular
powders. Examples of commonly used glidants
are magnesium stearate, starch and talc.
Reduction of particle size
Substances to be incorporated in a powder
are frequently milled to reduce particle size.
After milling the various substance are mixed
as needed.
Milling is the mechanical process for reducing
the particle size of solids before incorporation
into final products.
Advantages of milling
1- increases surface area which may increase
dissolution rate and bioavailability
2- facilitate drying of wet masses by increasing
surface area
3- improves mixing or blending of several solid
ingredients if they are reduced, to the same
particle size to minimize segregation and
provides greater dose uniformity
4- permits uniform distribution of coloring
agents in artificial colored solid pharmaceuticals
5- improves the function of lubricants used in
compressed tablets and capsules to coat the
surface of granules or powders
6- improves the texture, appearance, and
physical stability of ointment, creams and pastes
Disadvantages of milling
1- may change the polymorphic form of the
active ingredients, rendering it less active,
inactive or unstable.
2- may cause degradation of drugs as a result
of heat during milling, oxidation or adsorption
of unwanted moisture due to increased
surface area.
3-decreasing particle size may create static
charge problems that may cause particle
aggregation and decreasing dissolution rate.
4- increasing surface area may promote air
adsorption that may inhibit wetability of the
drug
Methods of particle size reduction
•On large scale, various mills are used e.g. the
rotary cutter, the hammer, and the roller mills
•On small scale the following techniques may
be used:
1- trituration
The substance is reduced to small particles by
rubbing it in a mortar with pestle
2- pulverization:
The substance is reduced and subdivided
with an additional material that can be
removed easily after pulverization is
complete.
As camphor which is pulverized with alcohol
or iodine with ether
Levigation
The substance is reduced in particle size by
adding a suitable non- solvent (levigating agent)
to form a paste in a mortar and pastle.
The method is used to incorporate solids into
dermatologic or ophthalmic ointments and
suspensions to prevent a gritty feel. Mineral oils
is a common levigating agent
Hammer mill
Fluid energy mill
Vibration mill
Mixing of powders
1-Spatulation:
Small amount of powders are blended by
movement of spatula through the powder on a
sheet of paper.
The method is not suitable for large
quantities of powder containing one or more
potent drugs because homogeneous blending
may not occur.
It is particularly useful for solid substances that
liquefy or form eutectic mixtures ( mixture that
melts at lower temperature than any of their
ingredients ) when in close and prolonged contact
with one another, since little compression or
compaction results.
2-Trituration:
It is used to comminute and to mix powders.
If comminution is desired, a porcelain mortar
with rough inner surface is preferred than glass
mortar with smooth working surface.
A glass mortar may be preferred for chemicals
that may stain the porcelain mortar and for
simple mixture of substances without need of
comminution.
2-
3-Geometric dilution
1. It is employed when a potent drug is to be
mixed with large amount of diluents.
2. The potent drug is thoroughly mixed by
trituration with an approximately equal
weight of the diluents in a mortar
3-A second portion of diluents equal weight
to the powder mixture in the mortar, is added
and trituration is repeated.
4-The process is continued, adding diluents
equal in weight to mixture in the mortar at
each step until all the diluents incorporated.
4-Sifting
During sifting, powders are mixed by passing
them through sifters
The process results in a light, fluffy product and
is generally not acceptable for incorporation of
potent drugs into a diluents base.
5-Tumbling
1. It is a process of mixing powders in large
container rotated on its axis by a motor
2. These blends are widely used in industry.
1-Tumbling mixers
Powders as a dosage forms
A-Bulk powders
They are dispensed by the pharmacist in bulk
containers; a perforated or sifter can for external
dusting, an aerosol container for spraying onto
the skin, or a wide mouthed glass container that
permits the entrance of the spoon and easy
removal of a spoonful of powder. Powders are
classified as:
1-Oral powders
The finely divided powders are intended to be
suspended or dissolved in water or other liquid.
Antacid and laxative powders are frequently
administered in this form.
2-Douche powders
They are generally dissolved in warm water by
the patient for vaginal use, although they may
be formulated for nasal, otic or ophthalmic
use.
3-Dentifrice or dental cleansing powders
Used in dental hygiene
4-Denture powder
Some are used as dentifrice powders and others
as adhesives to hold the dentures in place.
5-Triturations
They are dilution of potent powdered drugs,
prepared by mixing them with a suitable
diluents in a definite proportions by weight.
They were official as 1 – 10 dilutions.
6-Insufflations
•They are finely divided powders introduced into
body cavities as the ears, nose, throat, tooth
sockets and vagina by the aid of insufflators (
powder blower).
•Pressurized aerosols also have been used as a
means of administering insufflations especially
for the potent drugs.
7-Dusting powders
They are locally applied non- toxic
preparations that are intended to have no
systemic actions
They should be dispensed in a very fine
state of subdivision to enhance effectiveness
and minimize irritation.
They are applied to different parts of body as
lubricants, protective, adsorbents, antiseptics,
antipruritus, astringents and antiperspirants.
Although in most cases dusting powders are
considered non- toxic, the absorption of boric
acid through large areas of abraded skin has
caused toxic reactions in infants. Accidental
inhalation of zinc stearate powder has led to
pulmonary inflammation of the lungs of the
infants.
B-Divided powders
They are dispensed in the form of individual
dosed, generally in properly folded papers.
However, they may also be dispensed in metal
foil, small heat sealed plastic bags or other
containers.
After weighing, comminution and mixing of the
ingredients, the powder is divided into
prescribed number doses.
Special problems
Volatile substances as camphor, menthol or
essential oils may be lost by volatilization after
incorporation into powder. This problem is
prevented or retarded by using heat sealed
plastic or foil packets or by double wrapping
with waxed paper.
Liquids may be incorporated into divided
powders in small amounts. Magnesium
carbonate, starch or lactose may be added to
increase the adsorbability of the powder by
increasing the surface area.
When a liquid is a solvent for non – volatile,
heat stable compound, it may be evaporated
gently on water bath. Some fluid extracts and
tinctures may be treated in this way.
Hygroscopic substances that become moist
because of their affinity to moisture in air may
be prepared in divided powders by adding inert
diluents. double wrapping or foil packets
provide further protection.
Eutectic mixture: in order to diminish contact,
powder prepared from such substances is
commonly mixed in the presence of an inert
diluents such as light magnesium oxide or
carbonate to separate the trouble some agents.
Official powdered vegetable drugs
They are utilized in the preparation of
corresponding dosage forms:
•Powdered belladonna extract
•Powdered Ipecac
•Powdered opium
•Powdered digitalis
•Powdered cellulose is utilized as
pharmaceutical aid as a tablet diluents,
adsorbent, and suspending agent.
Official powders (USP)
•Absorbable dusting powders: used as
surgeon's gloves lubricant.
•Methylbenzethonium chloride powder: local
anti-infective powder used for diaper rash in
infants.
•Compound iodochlorohydroxyquin powder:
used as vaginal insufflations as antifungal.
•Nystatin topical powder: as topical dusting
powder in treatment of mycotic infections.
•Tolnaftate powder and aerosol: used in
treatment of fungal infection.