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 extensive.
may be blended with powdered
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
suitable wire
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 dosage form to ensure
dose-to-dose content uniformity
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
particles to the surface
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 sifter-
type 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

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

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

SLUGGING
compression of powder
into large tablets or
slugs on a
compressing machine
under 8,000 to 12,000lb
of pressure
Slugs: flat-faced and about 2.5cm(1in.) in
diameter
Granulated into the desired particle size,
for the production of tablets

Production of fines powder that has not
agglomerated into granules (separated,
collected and reprocessed)
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
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 CO2 masks
the undesirable taste of drugs.
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

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
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