Chapter 6: Powders and Granules

HISTORICAL USE

Powders convenient mode of

administering drugs derived
from hard vegetables such as
roots, barks, and woods
Used to administer insoluble
drugs
Calomel
Bismuth salts
Mercury
Chalk
As solid dosage forms, they
are used as internal and
external medications
INTERNAL USE
- They can be taken
orally through the
- Nose (snuffs)
- Blown to the body
cavity as insufflations
EXTERNAL USES
- Can be applied to
compromised areas of
the body
Also used to make solutions
for topical and oral use and
for use as douches
Other applications are
Powders containing a
bioadhesive material that
can be applied to a
specific body area

APPLICATIONS

Doses individually weighed,

placed in powder papers,
envelopes, small vials.
Infants who cannot swallow
tablets or capsules can accept
powders
Powders provide rapid onset of
action
They are readily dispersed
Have large surface area
Require only dissolution not
disintegration before absorption
Medicated powders in
therapeutics is limited
Use of powdered subs in
preparation is extensive
Powdered drugs maybe
blended with powdered
fillers to make tablets
May be dissolved or
suspended in solvents or
liquid vehicles
Incorporated to any
semisolid bases
Granules prepared
agglomerates of powdered
materials
- Used for medicinal
value
- Or making tablets

POWDERS
Composition:
-

Powders can be easily altered to

the quantity of medication for
each dose
Powders can also aid in clinical
studies of drug presentations,
dose can be easily adjusted

Uniform, small particle

size that has an
elegant appearance
- More stable than iquid
- Rapidly soluble
- Drug are absorbed
quickly
Properties of powders

 Related to the size and

surface area of the particles
Large particles = more
densed = tend to settle
more rapidly tan small
particles
Bulky particles = settle
more slowly
This should be considered in
mixing or storing and
shipping
Different particles size =
powders may be segregated
Powders should be
dispensed in tight container
because they have large
surface area,( large surface
area = they are exposed to
atmospheric conditions)
Small particle sized powders
= greater surface area to the
atmosphere = more reactive
in nature = adsorb larger
quantities of gases like
Carbon dioxide
Small particle size =
dissolve in more rapid
rate
But adsorbed gases from
nature could decrease
their wetting properties
Increase in surface free
energy = increase the
absolute solubility of the
drug = positive effect to its
bioequivalence

Topical powders are consist of:

Base or vehicle
cornstarch, talc
Adherent- magnesium
stearate, calcium
stearate, zinc stearate
Active ingredient
Aromatic material
Powder should provide large
surface area
- Flow easily
- Spread uniformly
Large surface are = aid in
absorbing perspiration and give
cooling sensation in the skin

INSUFFLATED POWDERS
-

TOPICAL POWDERS
Uniform, small particle size
that will not irritate the skin
when applied
Impalpable, and free flowing
Easily adhere to skin

Should not passed through

at least a No. 100-mesh
sieve to minimize skin
irritation
Highly sorptive powders not
used for topical powders that
are applies to oozing wounds,
they form hard crust
Hydrophobic, water repellent
powder prevent loss of water
from skin, will not cake on
oozing areas
Talc used to open
wounds, first sterilized to
avoid an infection in the
area

Finely divided powders

Applied in body cavity
(ears, nose, vagina,
tooth socket, throat)
When using insufflator or puffer
- Patient puffs the
desired quantity of
powder onto the after
area or cavity.

Tis is used as antiinfective

Polyox
-

Moisture-activated
adherent that is
incorporated into the
powder
Ethylene oxide
polymer, with high
molecular weight that
forms viscous
mucoadhesive gel
when in contact with
moisture
Serves to provide a
depot for long term
drug delivery
spanning several
hours.

PHYSICOCHEMICAL CONSIDERATIONS

Solid materials are first

characterized to determine their
chemical and physical features
including
- Morphology
- Purity
- Solubility
- Flowability
- Stability
- Particle size
- Uniformity
- Compatibility
Drug require chemical and
pharmaceutical processing

PARTICLE SIZE AND ANALYSIS

Particles of pharmaceutical
powders range from:
- Extremely coarse
(10mm) 1 cm in
diameter to
- Extremely fine
approaching colloidal

dimensions of
1micrgram or less.
United states pharmacopeia
(USP)
- Uses the ff:
Very coarse
Coarse
Moderately coarse
Fine
Very fine
- Related to the
proportion of powder
that is capable of
passing through the
openings of standard
sieves of varying
fineness in a specified
period while being
shaken, generally in
mechanical sieve
shaker.
Sieve opening are expressed in
millimeters or micron
Sieves are made of wire cloth
woven from brass, bronze, or
suitable wire. They are not
coated or plated

(SULAT MO NA YUNG SIVE SIZES BES)

Granules fall with range of 4

to 12-sieve

Granulations of powders
prepared in 12- to 20-sieve ->
used ffor tablet making
Dissolution rate of
particles intended to
dissolve drug
micronization = increase
drug dissolution and
bioavailability
Suspendability of
particles

 Uniform distribution of
drugs
Penetrability of particles
Lack of grittiness
METHODS TO DETERMINE PARTICLE
SIZE

Sieving
- particles are passed by
mechanical shaking through a
series of sieves of successively
smaller size.
Microscopy
sample particles are sized
thru the use of calibrated grid
background or measuring
device
Sedimentation rate
- determined by measuring the
terminal settling velocity of
particles thru a liquid medium in
gravitational or centrifugal
environment
stokes law
sedimentation rate
calculated
Light energy diffraction or light
scattering
- Determined by the
reduction in light
reaching the sensor as
the particle, dispersed
in a liquid or gas,
passes thru the
sensing zone
Laser scattering uses:
He-Ne laser
- Silicon photo diode
detectors
- Ultrasonic probe for
particle dispersion
Laser holography
- Pulsed laser is fired
thru an aerosolized
particle spray and

photographed in 3
dimensions with
holographic camera
allowing the particles
to be individually
imaged and sized
Cascade impaction
- Based on the principle
that a particle driven
by an airstream will
hit a surface in its
path , provided its
inertia is sufficient to
overcome the drag
force that tends to
keep it in the
airstream
Online methods

Single methods may be

sufficient

Combination methods
frequently preferred to provide
greater certainty of size and
shape parameters.

Most commercial particle size

analyzers automated and

linked with computers

Miromeritics study of small

particles
Reduction of particle size =
increases the number of
particles = total surface area

COMMINUTION OF DRUGS

Small scale reduces particle

size with the use of mortar and
pestle

Mortar with rough surface ( with

of liquid ( levigating agent)

porcelain mortar) = finer

which the powder is insoluble

- Paste is triturated,

grinding action
1. Trituration/ comminution
- Grinding a drug in a
mortar to reduce its

reducing the particle

-

size
The levigated paste

particle size
Large scale mills and

may be added to

pulverizers
FitzMill comminuting machine Thru the grinding action of

mixture made uniform

rapidly moving blades in the

rubbing them together

comminuting chamber, particles

with a spatula on the

are reduced in size and passed

thru a screen of desired
dimension to the collection
container
Collection or containment

ointment base and the

and smooth by

ointment tile.
Levigating agent
mineral oil and glycerin
BLENDING POWDERS
-

When two or more

system protects the

powdered substances

environment from a

are to be combined to

chemical dust, reduces

form a uniform

product lost, prevent

mixture
Best to reduce the

product contamination
2. Levigation
- Used in small scale

particle size of each

powder individually

preparation of

before blending and

ointments and

weighing
1. Spatulation
Blending small

suspensions to reduce
the particle size and

amounts of powders

grittiness of the added

powders.
Mortar and pestle or ointment

tile maybe used

Paste formed by combining
the powder and a small amount

by movement of a
spatula thru them on
a sheet of paper or an
-

ointment tile
Not suitable for large
quantities or potent
substances

Homogenous blending
is not as certain as

other methods
Very little compression

the mortar with the equal

from spatulation,

volume diluent and mixed

subs that form

eutectic mixture
(liquefy) when in close
and prolonged contact
with one another.
Mixed with inert
diluent ( light

equal in volume to the

mixture is added and
trituration repeat.
The process is repeated
until all diluent is
incorporated
- Add inert colored
powder to diluent

magnesium carbonate

before mixing to

to diminish contact

permit visual

comminute and to mix

by trituration
Second portion of diluent

magnesium oxide or

with eutectic mixture

3. Trituration
- Employed both to

of mixing is lacking
Process
Potent drug is placed in

or compacting result
suited for mixing solid

color and visible sign

inspection of mixing
process.
4. Sifting
- Mixing powders with

powders.
Glass mortar simple

use of passing thru

admixture without the special

sifters
Results in light fluffy

need for comminution

Geometric dilution small

product
Not acceptable for the

amount of a potent subs is to be

incorporation of

mixed with large amount of

potent drugs in the

diluent
-

Ensure the uniform

distribution of potent

drug
Indicated when potent
subs and other
ingredients are same

diluent drug
5. Tumbling
- Mixing powder in a
-

rotating chamber
Special small-scale
and large-scale
motorized powder
blenders

Mixing is thorough but

General guidelines to

time consuming
Blenders used in this

minimize/prevent segregation

1. Minimum number of transfer

process is used in
industry, they use
motorized blades to
blend powders in a

large vessel.
Segregation
- Undesirable

2.
3.
4.
5.
6.

distributor
7. Proper hopper design and
operating values

separation of the
different components
-

EUTECTICS
-

of the blend.
May occur by sitting

( dusting)
Fine particles tend to sift or

liquefy when mixed

together
To keep powders dry:

magnesium oxide or

and end up at the bottom of the

One can mix them with a bulky

powder adsorbent (light

percolate thru coarse particles

container and actually lift the

Powders become
sticky or pasty, may

or percolation
Air entrapment
(fluidization)
Particle entrapment

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

magnesium carbonate)
Powders should be triturated

larger particles to the surface.

Fine, aerated powders with

lightly on a pill tile by using

differences in particle size or

and pestle ( may cause

density = result in a striation

compression and make powders

pattern, occur in powder

sticky )
Double wrap the papers
Mixing them with bulky powders

transfer.
Dusting occur when

spatula for mixing rather mortar

first ad perform light blending

finer, lighter particles

remain suspended in air
longer and do not settle

absorb the paste that results

as quickly as the larger or

denser particles.

will reduce the problem

First make the eutectic and then

onto bulky powder

Dispensing the ingredients
separately.

potency differential between

HYGROSCOPIC AND DELIQUESCENT

the anhydrous and hydrated

POWDER

Hygroscopic powders absorb

moisture from the air

Deliquescent absorb moisture

form
Include a drying bulky powder
and use light, noncompacting
method of mixing the powder

from the air to the extent that

EXPLOSIVE MIXTURE

they will partially or wholly

liquefy.
Best approach is to dispense

the ingredients in a tight

INCORPORATION OF LIQUID

container and incorporate a

mixed

desiccant packet
Instruct the patient to store

ONTO INERT MATERIAL ( carrier) like

lactose or starch and geometrically

closed container
To lessen the problem dilute
the powder with an inert drying

introduced into the bulk of powder.

moisture
EFFLORESCENT POWDER
-

Crystalline powder

will dry out the paste

Best add a material by preparing
alcoholic solution and spraying evenly
to powder on the pill tile.
Alcohol or suitable solvent

that contains water of

will evaporate, leaving

hydration or

ingredient uniformly

crystallization.
Water could be
liberated during
manipulation or
exposure to low

humidity.
Powder become sticky and

Pasty material added to dry powder

by mixing with increasing quantities,

powder to reduce the amount of

surface area exposed to the

LIQUID THAT IS INCORPORATED

TO DRY POWDER CAN BE ADSORBED

it in a dry place in tightly

React violently when

pasty or liquefy
Use an anhydrous salt form of
the drug keeping in mind the

dispersed
This is suited for high
potency drugs
Minimizes the possibility of
clump of active ingredient
MEDICATED POWDERS
Internal used powder
- Taken orally after
mixing with water or

in case of infants in

The disadvantage is the

their infant formulas

Some are intended to

undesirable taste
Antibiotics for children-

be inhaled for local

intended for oral

systemic effects
Others are

administration as liquids but

unstable in liquid form
- Provided by

commercially
packaged for

manufacturer as dry

constitution
- Fro injection
- Vaginal douche
External use
- Dusted on affected

powders for
constitution with
-

area from sifter type

may remain stable for

container or applied

2 weeks
Sterile dry

from a powder aerosol

Labeled EXTERNAL
-

USE ONLY
Medical powders for oral use

or another suitable
solvent prior to

effects
Systemic effects
Counterpart to tablets
for patients who cant

administration by
injection
AEROSOL POWDERS

swallow them
Some are too bulky to

of dry powder inhalers

tablets
They can be mixed

( DPI) deliver
micronized particles of

with liquid or food

Powders taken orally for

medication in metered

systemic use may be

expected to result in a faster

Administered by
inhalation with the aid

be administered as
-

powders
Intended to be
constituted with water

may be
- Intended for local
-

water
The resultant product

quantities
DPI device used to

rates of dissolution and

administer an inhalation

absorption than solids =

powder in a finely divided

immediate contact with

state suitable for oral

gastric juices.

inhalation by patient.

 Inhalation powder used

Depression of device

with a device that

rubber bulb
- Cause turbulence of

aerosolizes and delivers

powder in vessel,

an accurately metered

forcing it out thru the

amount
- Used in asthma and

orifice in the tip

Inhalation

bronchial disorders
that requires

distribution of

active ingredient and

medication deep in
the lungs
Particle size of

finely divided solid

medication

state packaged in

prepared = 1-6

suitable container

micrograms in

closure system
Dose released from the

diameter
They contain

packaging by mechanism

inert

and mobilized into a fine

propellants and

dispersion upon oral

pharmaceutical

inhalation by the patient

diluents

The formulation may be packaged:

(crystalline,
alpha lactose
-

monohydrate)
Aid the formulations flow
properties and metering
uniformity and protect the
powder from humidity
Powders
blowers/
-

insufflators
Maybe used to deliver
dry powders to
various parts of body

the carrier
All formulation
components exist in

micronized

powder(DPI)
Consist of mixture of

Pre-metered DPI
Contain previously measured amount
of formulation in individual units
that are inserted into the device
before use
- Contain premetered
dose units as ordered
multidose assemblies
in the delivery
systems
Include a mechanism designed to
pierce the capsule or open the
unit dose container and allow

mobilization and aerosolization

the powder for measuring

of the powder by the patient

inhaling thru the integral
mouthpiece
Device- metered DPI
- Internal reservoir that

bulk = limited in nonpotent subs

Folded paper and packets
contains powders that are

contains sufficient quantity

supplied to patients in

of formulation for multiple

controlled dosage
Products are stored at clean, dry

place and room temp

Should be kept out the reach of

children and animal

Patients should be instructed

doses that are metered by

the device during actuation

the drug dose

Dispensing powder medication in

by the patient.
Dose counter and dose indicator
system
-

Incorporate a dosing

how to measure the appropriate

administration

dose and the type of vehicle

information

used to deliver the drug.

mechanism

DIVIDED POWDERS
-

Example of Oral Inhalation Powder

After powders are

( sulatin mo na lang to Meg)

blended by geometric

BULK AND DIVIDED POWDERS

dilution method for

Bulk powders

Antacids and laxatives which

individual dosing units

patient takes by mixing with

based on the amount

water or another beverages

to be taken at a single

before swallowing
Douche powders dissolved in

warm water by the patient for

vaginal use
Topical anti-infectives

contains B complex vit and other

nutritional supplements.
Small measuring scoop or
spoon- dispensed with

time.
Each divided portion is
placed in a small

piece of paper
Chartula Latin for

medicated powders for external

application to skin
Brewers yeast powder

potent subs
It is divided into

powder paper
Some available products
in folded papers are:
Headache powders
Powdered laxatives
Douche powders
Preparation:

Depending on the

potency f subs if
You weigh each portion of
powder separately before
enfolding in a paper
Approximate each portion

Glassine or vegetable parchment

limited barrier against moisture

is necessary
Waxed or glassine powders

containing volatile components

White bond paper powders

using the block-and-

containing neither volatile

divide method
- Used only for

components nor adversely

producing effects.

nonpotent drugs
Place te entire amount

out patient community

of powder in a tile
Forms a rectangle or

square with spatula

Cuts the powder

provided in this delivery systems are:

Compounded powders rarely used in

Commercial drug products that re

lengthwise or
-

crosswise
Each block = dose or
unit of medication

Powder papers used are:

(sulatin mo na lang size)
1. Simple bond paper
2. Vegetable parchment thin,
semiopaque paper, limited
moisture resistance
3. Glassine glazed, transparent

Polyethylene glycol

3350
Cholestyramine resin
Pectin
L-glutamine
Sodium

phenylbutyrate
Wheat dextrin

Composed of dry

GRANULES
agglomerates of

paper, limited moisture

powder particles that

resistance
4. Waxed paper transparent

may contain API, with

or w/o other

waterproof paper
What to use?

dispersed in food,

Hygroscopic or deliquescent
waxed paper or water proof
- Double wrapped and

dissolved in water
Frequently compacted
into tablets or filled

wrapped again with

bond paper

ingredients.
May be swallowed,

into capsules
Irregular in shaped,
spherical

4- to 12 mesh sieve

- processes fine powder

range

into dense sheets by

Method of preparation

forcing it thru two

1. Wet methods
2. Dry methods

mechanical rotating
metal rolls running

Wet methods:

counting to each other

- surface may be smooth

Basic wet method

- Moisten the powder
- Pass the resulting paste

or has pockets.
- Compacted powder =

thru a screen of the

granulated to uniform

mesh size t produce

particle size in a

the desired size of

mechanical granulator
Powder compactors

granules
- Place it in drying plates,
dry by air or heat
- Periodically remove
granules to prevent
adhesion into large

combined in sequence
integrated compactorgranulation system
Alternative dry
method/slugging
- Compression of a

mass
Fluid bed processing
- Particles are placed in a

powder or powder
mixture into tablets or

conical piece of

slugs on a

equipmemt and

compressing machine

vigorously dispersed

under 8,000 to 12,000

and suspended while

lb of pressue
Slugs generally flat

a liquid excipient is
sprayed on the

faced and about 2.5 cm

particles and product

in diameter
- Granulated into desired

dried, forming
granules or pellets

particle size used in

Dry Methods: Dry granulation method

tablets

dry powder is passed thru a roll

Dry process results in fines (powder

compactor and then thru a

that has not agglomerated into

granulating machine
roll compactor or roll

granules)

press or roller compactor

- Fines are separated,

collected, reprocessed

Granules

effervescent prior to
- Flow well compared to
powders
- Used in tablet making

ingestion
Effervescent salts granules or
coarse to very coarse powders

to facilitate free flow

contains medicinal agent I a dry

from feeding

mixture

container (hopper)
- Into tablet presses
Surface are is less than
powder = more stable to
the effects of

- Composed of citric acid,

tartaric acid, sodium
bicarbonate
- Makes undesirable taste
Using granules or coarse

atmospheric humidity =

particles of mixed powder

less likely to cake

- Granules are easily

= decreases rate of soln

wetted by liuids
Some commercial prod containing

= prevents violent
effecrvescence
Combination of citric acid

antibiotic drugs unstable in aqueous

+ tartaric acid less

soln = prepared as small granules for

probem
Tartaric acid alone =

constitution.
Granules are prepared
not only medicinal agent

granules readily lose their

firmness and crumble
Citric acid alone = sticky

but with colorant,

flavorant and others
(yung example sulat mo na lang bes)

Granular dosage form are used

in veterinary meds

EFFERVESCENT GRANULATED SALTS

Effervescent dosage form

tablets or granules, contains
ingredients, that release
carbon dioxide when in
contact with water.
- Dissolved or dispersed
in water to initiate

mixture
Preparation
1. Dry or fusion method
- One molecule of water
present in each molec
of citric acid acts as
binding agent for the
powder mixture.
- Citric are powdered,
mixed with other
powder of the same
sieve size (ensure
uniformity)

 Equipment should be
made of stainless steel to
resist acids
- Mixing of powder is
rapid in low humidity
environment to
prevent absorption of
moisture

- After mixing, put on a

suitable dish