 The term powder has more than one use in pharmacy:

◦ May describe the physical form of a material: a dry substance

composed of finely divided particles
◦ May describe a type of pharmaceutical preparation: medicated powder
intended for internal or external use
 Physical and chemical characterization is required before
the use of powders in the preparation of a pharmaceutical
formulation:
◦ Morphology
◦ Purity
◦ Stability
◦ Particle size
◦ Uniformity
◦ Compatibility with other excipients or drugs
 The particles of pharmaceutical powders may range from 10
mm to ≤ 1 m
 Descriptive terms used by the USP:
◦ Very coarse
◦ Coarse
◦ Moderately coarse
◦ Fine
◦ Very fine
 Powder of vegetable and
animal drugs are officially
defined as follows:
 Provides quantitative data on:
◦ Size
◦ Distribution
◦ Shape or morphology of a drug or other components to be used in
pharmaceutical formulation
 All the above may influence a range of pharmaceutical
properties which are important technologically and
biopharmaceutically
 Granules typically fall within the range of 4- to 12- sieve size
 Granules of powders prepared in the 12- to 20- sieve range
are used in tablet making
 Dissolution rate of a drug
 Suspendability (floating) in suspension making
 Uniform distribution of a drug substance in a powder
mixture (ensure dose-to-dose content uniformity)
 Penetrability (deposition) of particles (e.g., inhalers)
 Lack of grittiness in topical and ophthalmic preparations
 Syringe-ability
 Analytical methods used for the determination of particle size:
◦ Analytical sieving
◦ Sedimentation
◦ Coulter counter
◦ Microscopy
 Sampling process:
◦ Using a powder sampler (thief)
◦ The thief is immersed in the container until touching the bottom
 To obtain a representative sample of the powder
 Selection of the optimal quantity of powder sample for
sieving analysis:
 Two approaches are available (see next slide):
◦ Relating the quantity of powder with its density:
 If we have a powder with density = 1.5 g/mL, we can use 25 g of powder for
each sample
 If we have a powder with density > 3 g/mL, we can use 100 g of powder for
each sample
◦ The second approach makes reference to the mean dimension of
the powder
 If the sampled quantity is large for particle size analysis, it
is divided in the following manner (see figure):
◦ Make a powder heap with a cone shape
◦ Crack the powder cone until reaching about 1/3 of its initial height
◦ Divided the cone into 4 parts
◦ Take the two opposite parts
◦ Mix the obtained parts and make another cone
◦ Repeat the above operation for a number of times until obtaining an
optimum amount of powder for the analytical process
 Why is it important to obtain the right quantity of powder for
sieve analysis?
◦ Excessive quantity of powder:
 Can deform the mesh of the sieve
 Does not permit regular flow of the powder over the mesh of the sieve
 Results in incorrect powder classification
 The sieving process should be carried out automatically to
be reproducible
◦ With automatic sieving (6 – 8 sieves placed one over the other from
the higher to the lower sieve)
◦ A powder sample of 100 g is placed in the upper sieve, the cover is
closed
◦ The system is shaken for 5 min, normally the process can be
stopped if within 1 minute no more than 0.1% of the powder passes
◦ At the end of the process, the powder sample will be distributed
between the sieves according to their diameter
 Sieving video
 https://www.youtube.com/watch?v=M8cqAjXUhLc
 The velocity of sedimentation can be calculated by the use of
Stokes’ Law
◦ V = h/t
◦ h is the distance traveled by the particle during the time t
 Stokes’ law is summarized in the following formula:
 Stokes’ law:
◦ d is the average diameter of the particles
◦  is the viscosity of the medium in poises
◦ h is the height of fall in the time t
◦  is the particle density
◦ 0 is the density of the disperse material
◦ g is the gravity acceleration
 This law is valid only for diluted suspension (0.5 – 2%) of
the spherical bodies
 Examples of the methods that use the sedimentation
principles:
◦ Andreasen pipette
 Barium sulfate particle size analysis:
◦ Used as a contrast media for the X-rays examination of the GIT
◦ One of the requirements for this use is that the powder must be very fine to avoid
its rapid sedimentation in the GIT
 The testing procedure is as follows:
◦ Put 5 g of BaSO4 in a 50 mL cylinder
◦ The cylinder is provided with emery stopper, and it is graduated from 0 to 140
mm
◦ Fill to the desired volume with water and mix for 5 minutes
◦ Leave it to settle for 15 minutes.
◦ The BaSO4 must not precipitate under 15 mm
 Coulter counter:
◦ Counts the particles and classifies them in different dimensional
classes
◦ Permits the measurement of the volume of the particles directly using
the conductometric method
 Principle:
◦ A typical Coulter counter has one or more microchannels that separate
two chambers containing electrolyte solutions
◦ As fluid containing particles or cells is drawn through each
microchannel, each particle causes a brief change to the electrical
resistance of the liquid
◦ The counter detects these changes in electrical resistance
 Video on Coulter counter
 https://www.youtube.com/watch?v=oaU1ZO41dpY
 Advantages of the Coulter counter method:
◦ What is unique about this method that it
measures a property (change in electric signal),
which is directly related to the volume of particles
◦ The results are given in terms of particle
volumes; thus it is easy to calculate the diameter
of a sphere of equivalent volume

4 3 3v
v  r  r 3
3 4
◦ v is the volume of a sphere that has r radius
 Advantages of the Coulter method:
◦ Rapid operation: a single calculation requires only 30 seconds
◦ It is possible to count a high number of particles and obtain more
acceptable results
 The high cost is the main disadvantage of this method
 With the use of the microscope we can evaluate forms and
dimensions of the particles
 Disadvantages:
◦ In order to have a reasonable statistical results we have to examine not
less than 300-500 particles
◦ Good results are achieved when the number of analyzed particles is
increased to 3000
◦ Therefore, considered slow and difficult
 Choice of the particles diameter

 Normally it is preferable to give the diameter of the circle,

which has the same area of the particle

Area    r 2
 With the optical microscope, we can analyze particles with
diameter in the range of 0.5 – 1000 m
 The analytical procedure:
◦ Prepare a very diluted suspension of powder
◦ Place the suspension on a glass slide
◦ Cover with another slide
◦ Observe with the help of micrometer (helps in the measurement of
the diameters of the particles)
◦ Count and classify the particles with diameter included into a
selected range
 Flowability (angle of repose, glidants)
 Dustiness
 Compressibility
 Cohesiveness
 Porosity and void
 Why is it important?
◦ In tableting machines, the dosage of powders is volumetric
◦ A rotating die passes under the powder funnel (hopper), the die is then
filled, and the contents are compressed to obtain the desired tablet
 Why it is important?
◦ It is important to know:
 The exact volume of powder to fill the die to reach the desired weight
 The exact time to reach the minimum volume in the die
 The time necessary to have an exact fill of the die
◦ These values depend on the flow rate of the powder
 Video on tableting
 https://www.youtube.com/watch?v=g4rrGMJqEdk
 Important to know:
◦ The time required for powder to reach the minimum volume into the
die (called shaking volume)
◦ The time required for the die to be filled in an optimum manner
 Disadvantage of poor powder flow:
◦ Incomplete and/or irregular filling of dies or bottles
 Advantages of good powder flow:
◦ The shaking volume (minimum fill) is reached in a very short time
◦ Dies and containers can be filled in very short time
◦ Complete and consistent filling of dies or bottles
 Factors that decrease the flow of powder
◦ Superficial adhesivety
◦ High specific surface: high area, decrease in flowability
◦ Particle shape: spherical particles flow faster than irregularly-
shaped particles
◦ Surface of particles: particles with wrinkled surfaces flow slower
than those with smooth surfaces
◦ Presence of electrostatic charges on the surface of the particles
◦ Hygroscopicity of the powders
 Testing methods:
◦ Flow through an orifice
◦ Angle of repose ()
Flow through an orifice
 By measuring the flow rate of powder through an orifice:
◦ How to?
 Fill a cylinder with the powder (a cylinder provided with an orifice with
predetermined diameter see USP)
 Measure the powder quantity that flows out from the orifice in the unit of
time
 Express the flux velocity as g/minute
 The powder flow velocity does not depend on the height of
the powder, which is present in the cylinder, as long as the
powder stays at height from the orifice (powder head),
which is many times higher than the diameter of the orifice

◦ d is the diameter of the orifice

v d
flux
◦ a = 2.6 in the case of ideal pharmaceutical powders
a
 Video on powder flow
 https://www.youtube.com/watch?v=mMsDK0myWkk
 Factors affecting flow rates through an orifice:
◦ Orifice diameter
◦ Hopper width
◦ Head size (powder depth)
◦ Hopper wall angle
 Angle of repose:
 How to?
◦ The powder flows from a semi-cylinder or from a funnel
◦ The powder flows in a petri dish, the formed powder cone is then
evaluated
 Angle of repose
◦ The angle formed between the surface of the cone and its base
Tan = h/r
 The cone:
◦ The faster the powder flows, the lower the height of the formed cone
◦ Adhesive powders (poorly flowable) form very sharp and tall cones
◦ Angle of repose ()
 Tan  is equal to the height of the cone (h), divided by the
radius of the base of the cone (r)
 From the tangent of the angle, the value of the  is obtained
 As a general rule, powders with  ≥ 50, have unsatisfactory
flow properties, whereas  close to 25, have very good flow
properties
 Angle of repose: variations:
◦ By varying the height of the funnel or the width of the base, cones with
different heights can be obtained
◦ See Table 12.1
◦ Drained angle of repose
 Drained angle of repose:
◦ The Petri dish is placed on a stand into a box, the box is completely
filled with the powder
◦ The box has a transparent side, which permits viewing the inside
◦ The lower side of the box has a window (an orifice) through which
the powder flows out
◦ In this manner, we do not have the problem of variation of the cone
shape due to the effect of kinetic energy
◦ At the end of the experiment, the tang  of the obtained powder
cone is calculated
 Video on the angle of repose
 https://www.youtube.com/watch?v=mpf1wxG0R7c
 https://www.youtube.com/watch?v=7UM5R-oMBHc&t=14s
 How is the poor flow problem solved?
◦ Glidants:
 Flow enhancers improve the flowability of powders by reducing inter-particle
friction
 Excipients that have anti-adherent or lubricant properties may enhance powder
flowability
 Usually, glidants are hydrophobic substances
 Examples:
◦ Talc
◦ Mg stearate
◦ Starch
◦ Silica gel, (Aerosil)
 If poor flow is due to the humidity or hygroscopicity, the use
of the MgO and SiO2 is advisable
 High levels of hydrophobic glidants can:
◦ Decrease disintegration of tablets
◦ Decrease dissolution of the active material
 Minimum quantity of glidant should be used
 Level of glidant and flowability:
◦ Initially the flow rate increases with increasing glidant concentration
until reaching a maximum value, after which the flow velocity will
decrease
◦ The ideal quantity of glidant can then be determined
◦ Normally glidant concentration that is used to give the best flow rate is
in the average of 1-2%
 Dustiness
◦ The tendency of fine particles to separate from the main bulk of
powder and then be dispersed into the atmosphere during product
movement
 Dustiness affects:
◦ The safety of personnel and plant (explosion risk)
◦ Working conditions and health of workers (allergy, respiratory
disorders)
◦ The control of the product (wastage, cross contaminations)
 Electric surface properties:
◦ The electrostatic behaviors of the powders can also be the origin of
unwanted phenomena
◦ Installations becoming electrically charged, and in some cases,
explosions
 Compressibility:
◦ Compressibility is calculated by the formula:

◦ (Carr’s index)
◦ ad = apparent density
◦ td = tapped density
 Compressibility:
◦ If the compressibility is low < 20%, the product flows freely
◦ If the compressibility is high (> 40%), the product packs and has a
tendency to bridge in silos (structures for storing bulk materials)
 Cohesiveness:
◦ Cohesiveness is calculated by the formula:

◦ Hausner ratio
 Cohesiveness:
◦ Low cohesiveness (< 1.25) reflects the ability of the product to flow
easily in transfer systems
◦ High cohesiveness (> 1.4) leads to blockage of the powder in transfer
systems or to clogging
 Porosity, void, and volume
 Void
◦ If particle size is not uniform, smaller particles will slip into the spaces
between larger particles and decrease the void areas
◦ Packing and flow are important, as they affect:
 The size if container required for packaging
 The flow of granulations
 The efficiency of the filling apparatus for making tablets and capsules
 The ease of working with the powders
 True volume of a powder (V)
◦ The space occupied by the powder exclusive of all voids that not are
fundamental part of the molecular packaging arrangement
 Bulk volume of a powder (Vbulk)
◦ Includes the contribution of interparticulate void volume
 Void can be defined as:

Vbulk  V
 Porosity is
Vbulk

Vbulk  V
x100
Vbulk
 Porosity
◦ The percentage of the volume occupied by pores and free spaces
◦ Porosity () is:
Void x 100
 The bulk volume = true volume + porosity
 Apparent density and true density:
◦ Apparent density (a):

Weight of the Sample

◦ True density () is: Vbulk

Weight of the sample

V
 In pharmacy:
◦ The pharmacist reduces the size of powder by grinding in a mortar and
pestle
◦ A finer grinding action is accomplished by using a mortar with a rough
surface (as a porcelain mortar)
◦ A glass mortar has a smooth surface
 Trituration is grinding of a drug in a mortar to reduce its
particle size
 On industrial scale, various types of mills and pulverizers may
be used to reduce particle size
 See industrial pharmacy
 Levigation (used for small-scale preparation) of ointments
to reduce the particle size and grittiness of added powders
 Tools that are used include mortar and pestle or an
ointment tile
 A paste is formed by combining the powder and a small
amount of liquid (levigating agent) in which the powder is
insoluble (?)
 Methods used to blend powders:
◦ Spatulation
◦ Trituration
◦ Sifting
◦ Tumbling
 The method is chosen based on the:
◦ Nature of the ingredients
◦ Amount of powder
◦ Equipment
 Spatulation
◦ Used to blend small amounts of powders by movement of a spatula
through them on a sheet of paper or an ointment tile
◦ Not suitable for mixing large quantities of powders or for powders
containing potent substances because homogeneous blending is not
ensured as some other methods
 Why is spatulation suitable to mix solid substances that
form eutectic mixtures (or liquefy) when they come in close
and prolonged contact with one another?
◦ Very little compression or compaction of the powder results from
spatulation
◦ To diminish contact, a powder prepared from eutectic mixtures is
commonly mixed in the presence of an inert diluents such as:
 Light MgO or
 MgCO3
◦ This will separate the interacting agents physically
 Substances that form eutectic mixtures when combined
include:
◦ Phenol
◦ Camphor
◦ Menthol
◦ Thymol
◦ Aspirin
◦ Phenyl salicylate
 Trituration
◦ Used to comminute and mix powders commonly performed using a
mortar and pestle
◦ If simple mixture is desired without special need for comminution, a
glass mortar is recommended
 Geometric dilution:
◦ Used when a small amount of a potent substance is to be mixed
with a large amount of diluent
◦ When the potent ingredient and other ingredients have the same
color and a visible sign of mixing is lacking
◦ To ensure the uniform distribution of the potent drug
 Blending procedure with geometric dilution:
◦ The potent drug is placed with an approximately equal volume of
the diluent in a mortar and mixed thoroughly by trituration
◦ Then a second portion of diluent equal in volume to the mixture is
added, and the trituration repeated
◦ Repeat adding equal volumes of diluent to the powder mixture and
repeating until all of the diluent is incorporated
 Why some pharmacists add an inert colored powder to the
diluent before mixing?
◦ To permit visual inspection of the mixing process
 Sifting: the blending of powders by:
◦ Passing them through sifters like those used in the kitchen to sift flour
◦ Sifting results in a light, fluffy product
◦ Not acceptable for the incorporation of potent drugs into a diluent
powder
 Tumbling:
◦ The tumbling (moving up and down) of the powder in a rotating
chamber
◦ Special small-scale and large-scale motorized powder blenders mix
powders by tumbling action
◦ Mixing is thorough but time-consuming
◦ See industrial pharmacy
 Intended to be used internally or externally
 Most powders for internal use are taken orally after mixing
with water
 Some powders are intended to be inhaled for local and
systemic effects
 Other dry powders are commercially packaged for constitution
with a liquid solvent or vehicle
 Some for administration as:
◦ Oral
◦ Parenteral
◦ Vaginal douche
 Medicated powders for
external use are dusted on
the affected area from a:
◦ Sifter-type container or
◦ Applied from a powder
aerosol
 Powders intended for
external use should bear a
label marked “for external
use only”
 Medicated powders for oral use may be intended for:
◦ Local effects (e.g., laxatives)
◦ Systemic effects (e.g., analgesics)
 Advantages of medicated powders compared to tablets and
capsules:
◦ May be preferred by patients who have difficulty swallowing solid
dosage forms
◦ The dose of some drugs is too bulky to be formed into tablets or
capsules of convenient size
◦ Faster rates of dissolution and absorption
◦ Antibiotics for children, are intended for oral administration as
liquids but are relatively unstable in liquid form
 Antibiotics for children:
◦ Are provided to the pharmacist by the manufacturer as a dry powder or
granule for constitution with a specified quantity of purified water at
the time of dispensing
◦ The resultant product remains stable for the prescribed period of use,
generally up to 2 weeks (depending on storage temperature)
 Some medicated powders are administered by
inhalation with the aid of dry powder inhalers
 Inhalers deliver micronized particles of medication in
metered quantities
 Most of these products are used in the treatment of:
◦ Asthma
◦ Other bronchial disorders that require distribution of active
ingredient deep in the lungs
 To achieve the best deposition inside the lungs, the particle
size of the drug is prepared in the range of 1 to 6 m in
diameter
 These products contain:
◦ The therapeutic agent
◦ Inert propellants
◦ Pharmaceutical diluents (e.g., -lactose).
 -lactose:
◦ Improves the formulation's flow properties
◦ Aids in metering uniformity
◦ Protects the powder from humidity
 Powder blowers or insufflators are used to deliver dry
powders to various parts of the body
 Depression of the device's rubber bulb causes turbulence of
the powder in the vessel, forcing it out through the orifice in
the tip
 Medicated powders may be provided to the patient in bulk or
divided forms
 Some powders are packaged by manufacturers
 Others are prepared and packaged by the pharmacist
 Limited to non-potent substances such as:
◦ Antacids and laxatives
 Intended to be mixed with water or other beverage before swallowing
◦ Douche powders
 These are dissolved in warm water by the patient for vaginal use
◦ Medicated powders for external application to the skin
◦ Brewer's yeast powder containing B-complex vitamins and other
nutritional supplements
 A small measuring scoop, spoon, or other device is
dispensed with the powder for measuring the dose of the
drug
 These contain potent
substances that should be
administered in controlled
dosage
 Each divided portion of powder
may be placed on a small piece
of paper (Latin chartula)
 The powder paper is folded to
enclose the medication