CHAPTER 6

POWDERS & GRANULES

41 Tecson
42 Tuazon
43 Ubana

POWDERS
physical form: a dry substance
composed of finely divided particles.
type of pharmaceutical preparation:
medicated powder intended for
internal or external use.

Powders are intimate mixtures of

dry, finely divided drugs and/or
chemicals that may be intended for
internal or external use.

the use of medicated powders in

preparation of other dosage forms is
may
be blended with powdered
extensive.
fillers and other pharmaceutical
ingredients to fabricate solid
dosage forms as tablets and
capsules

the use of medicated powders in

preparation of other dosage forms is
extensive.

may be dissolved or suspended

in solvents or liquid vehicles to
make various liquid dosage forms.

the use of medicated powders in

preparation of other dosage forms is
extensive.
may
be incorporated into semisolid
bases in the preparation of
medicated ointments and
creams.

Particle Size and

Analysis
USP uses descriptive terms to
characterize particle size
-very course -fine
-course -very fine
-moderately course
Sieves- generally made of wire cloth
woven from brass, bronze or other

Purpose
obtain quantitative data on the size,
distribution, and shapes of the drug and
other components to be used in
pharmaceutical formulations

Important factors that a

particle size can influence

Drug micronization can increase the

rate of drug dissolution and its
bioavailability

Suspendability of particles intended

to remain undissolved but uniformly
dispersed in a liquid vehicle
Uniform distribution of a drug
substance in a powder mixture or solid

Penetrability of particles intended to be

inhaled for deposition deep in the respiratory
tract
Lack of grittiness of solid particles in
dermal ointments, cream, and ophthalmic
preparations

Methods for
determining particle
size
Sieving passed through a series
of sieves

 Microscopy sized through

the use of calibrated
grid background

Sedimentation Rate
- measuring the terminal
settling velocity through a
liquid medium in a gravitational
environment - Stokes Law

Light energy diffraction

reduction in light
reaching the sensor as the particle,
dispersed in a liquid or gas, passes
through the sensing zone
Laser Holography pulsed
laser is fired through an
aerosolized dimensions
with a holographic camera

 Cascade Impaction
separated into various size
ranges by successively increasing
the velocity of the airstream in
which they are carried
*a reduction in particle size increases
the number of particles and the total
surface area

Comminution of Drugs
Small Scale:
Trituration grinding a drug
in a mortar to reduce its particle
size
Levigation preparation of
ointments and suspensions
to reduce particle size and
grittiness of the added powders

Large Scale:

Mills and Pulverizers FitzMill

grinding action of rapidly moving
blades, particles are reduced in
size and passed through a screen
of desired dimension to the
collection container

Blending Powders
Spatulation blending
small amounts of powders by
movement of a spatula

Trituration may be employed

both to comminute and to mix
powders

 Geometric Dilution mixing a

small amount of potent substance
with a large amount of diluent /
ensure the uniform distribution of the
potent drug

 Sifting powders are passed

through sifters, resulting in a light
and fluffy product
Tumbling tumbling
the powder in a
rotating chamber

Segregation undesirable
separation of the different
components of the blend
Occurs by sifting or percolation,
air entrapment (fluidization),
particle entrapment (dusting)
Fine particles tend to sift or
percolate through course particles
and end up at the bottom of the
container and lift the larger

Dusting occurs when the finer, lighter

particles remain suspended in air longer and
do not settle as quickly as the larger or denser
particles.

Guidelines to minimize/ prevent

segregation
Minimum number of transfer steps
and drop heights
Control of dust generation
Control of fluidization of powder
Slow fill/ transfer rate
Appropriate venting

 Use of a deflector, vane or

distributor
Proper hopper design and operating
valves

Medicated Powders
Can be taken:
1. Internally
2. Externally

INTERNALLY
Taken orally after mixing with water (or in
milk formulas in the case of infants)
*reconstitution
Can be inhaled for local or systemic
effects
or

EXTERNALLY
Dusted on the affected area from a siftertype container
Applied from a powder
aerosol
Should bear the label
EXTERNAL USE
ONLY

ADVANTAGES
*For patients who have difficulty in
swallowing tablets or capsules
Drugs are too bulky to be formed as
tablets
May be expected to result in FASTER
RATES of dissolution and absorption than
solid dos. forms

DISADVANTAGE
*May be undesirable in taste
*Unstable in liquid form (in which case, the
manufacturer will
distribute it as dry powders
for constitution; stable for
max of 14 days)

AEROSOL POWDERS
*Powders that are administered by
inhalation
*With aid of DRY-POWDER
INHALERS-delivers micronized
particles of medication in
metered quantities
*Most are used in the treatment of asthma
and other bronchial disorders

1 to 6 mcm- (in diameter) particle size of

micronized medication.
Crystalline alpha-lactose monohydrate
- Pharmaceutical diluent that aids in
formulations flow properties and protects
from humidity.

Powder blowers or insufflators

-may be used to deliver powders to
various parts
of body.

BULK AND DIVIDED

POWDERS
BULK POWDERS:
a) Antacid
b) Douche powders
c) Med powders for external applic.
d) Brewers yeast powders

-limited to nonpotent substances

-stored at room temp in a clean, dry place.
-kept out of reach of children and animals

DIVIDED POWDERS
-for potent substances
-ready to take
-in a variety of small pieces of paper
(chartulae)

Commercially available products:

BC powders- for headache
Psyllium mucilloid- laxative
Massengill powder rackets-douche
powders

Method of preparation:
*weigh each portion of powder separately
before enfolding in a paper
*bock-and-divide method (for nonpotent
subs only)

Types of papers used:

a) Vegetable parchment -semi-opaque,
moisture resistant.
b) White bond paper- opaque, no
resisting properties
c) Glassine-glazed, transparent, moisture
resistant
d) waxed- transparent waterproof

Folding of powder paper

Granules
prepared agglomerates of
powdered materials
used for the medicinal value of their
content
used for pharmaceutical purposes
(making tablets, etc.)

Granules
flow well compared to powders
more stable to atmospheric humidity
less likely to cake or harden upon
standing

Irregularly shaped but

may be prepared to be
spherical
Usually in the 4- to 12-mesh sieve size
range
Prepared by wet and dry methods

WET METHOD
May be done in 2 ways:
basic wet method
fluid bed processing (preblending, granulation,
drying)

Application: drugs which are stable with moisture;

for powdered materials which are not compressible

WET METHOD
Moisten the powder (powder mixture) and then pass the
resulting paste through a screen of the mesh size to
produce the desired size of granules

WET METHOD
Granules are placed
on drying trays and
dried by air or heat.

WET METHOD
Fluid bed processing particles placed on a
conical piece of equipment, 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.

DRY METHOD
powder mixture is compacted in large pieces &
subsequently broken down & sized into granules
may be done in 2 ways:
roller compactor & granulating machine
Slugging

Application: heat & moisture- sensitive drugs

ASA, Vit C, Vit B1

DRY METHOD
Passed through
a roll compactor
(roll press)
process a fine
powder into dense
sheets by forcing it
through two
mechanically
rotating metal rolls
running counter to
each other.

DRY METHOD
SLUGGING
compression of powder
into large tablets or
slugs on a
compressing machine
under 8,000 to 12,000lb
of pressure

DRY METHOD
Slugs: flat-faced and about 2.5cm(1in.) in
diameter
Granulated into the desired particle size,
for the production of tablets

DRY METHOD
Production of fines powder that has not
agglomerated into granules (separated,
collected and reprocessed)

EXAMPLES
Biaxin granules (clarithromycin,
oral suspension)
Omnicef (cefdinir, oral suspension)
Augmentin ES-600 (amixicillin/
clavulanate K)
Ceftin (cefuroxime axetil, Oral
suspension)
Lactinex granules (lactobacillus
acidophilus, lactobacillus bulgaricus)
treatment of uncomplicated
diarrhea and diarrhea due to
antibiotic therapy
Zantac EFFERdose tablets
compressed granule effervescent

EFFERVESCENT
GRANULATED SALTS
granules of coarse to very coarse powders
containing a medicinal agent in a dry mixture
composed of
sodium bicarbonate
citric acid
tartaric acid

effervescence from the released CO 2 masks

the undesirable taste of drugs.

EFFERVESCENT
GRANULATED SALTS
tartaric acid alone -granules readily lose their
firmness & crumble

citric acid alone - results in a sticky mixture which is

difficult to granulate

prepared by:
dry or fusion method
wet method

Dry or fusion method

One molecule of water present in each
molecule of citric acid acts as the binding
agent for the powder mixture
Granules are dried not exceeding 54C and immediately
placed in tight sealed containers
Acetaminophen for Effervescent Oral Solution USP

WET METHOD
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 pliable mass for
granulation

examples

QUESTIONS