Aira Jhamaica Dimacale

Pharmaceutical Dosage
Chapter 6: Powders and Granules

Made of wire cloth woven (not coated or

plated) from brass, bronze, and other suitable
wire

Granules

Powders

Prepared agglomerates of powdered particles

Intimate mixtures of dry, finely divided drugs and/or

chemicals used externally or internally

Contain one or more active ingredients with or

without other ingredients

Medicated powder:

4-12 sieve size range

Granulations of powders used in tablet making

(12-20 sieve range)

Internal use: oral powder

External use: topical powder

Uses of Medicated Powders in Therapeutics

To fabricate solid dosage forms as tablets and capsule

To make various liquid dosage forms

Blended with powdered fillers and other

pharmaceutical ingredients

Dissolved or suspended in solvents or liquid

vehicles

Incorporated into semisolid bases

Medicated Powders

Sieve Number

Sieve Opening

Sieve Num

2.0

9.50 um

70.0

3.5

5.60 um

80.0

4.0

4.75 um

100.0

8.0

2.36 um

120.0

10.0

2.00 um

200.0

20.0

850.00 um

230.0

30.0

600.00 um

270.0

40.0

425.00 um

325.0

50.0

300.00 um

400.0

60.0

350.00 um

To prepare medicated ointments and creams

Opening of Standard Sieves

Internal use:

Taken orally after mixing with water

Some are inhaled for local effects (laxatives) or

systemic effect (analgesic)

External use:

Dusted on the affected area from sifter-type

container or applied from powder aerosol

Particle Size and Analysis

Characterized to determine their chemical and physical

features before the preparation of pharmaceutical
products including:

Morphology, purity, solubility, stability,

particle size, uniformity, compatibility with any
other formulation components

For efficient production of a finished dosage form:

optimum therapeutic efficacy, adjustment and control of
powders particle size

Definition of Some Terms

Extremely coarse: about 10 mm to 1 cm in

diameter

Extremely
fine:
approaching
dimensions of 1 micron or less

Should bear a label marked external use only

Solid Materials

Particles of pharmaceutical powders range from:

colloidal

Micromeritics

Science of small particles

Characteristics included: particle size, angle of

repose, bulk volume, size distribution, porosity,
apparent density, shape, true volume, bulkiness

USP Standings for Powders of Animals and Vegetable Drugs

USP Descriptive Terms

Sieve Size: All Particles Pass T

Very Coarse (No. 8)

Coarse (No.20)

20

Sieves

For pharmaceutical testing and measurement,

reduction of particle size of powders

Moderately Coarse (No.40)

40

Fine (No.60)

60

Very Fine (No.80)

80

Purpose of Particle Size Analysis in Pharmacy

To obtain quantitative data of drug and other components

used in pharmaceutical formulations on the size,
distribution, and shape

Variety of Important Factors Particle Size can Influence

Dissolution rate of particles

Intended to dissolve

Drug micronization increases rate of drug

dissolution and its bioavailability

Suspendability of particles

Intended to remain undissolved but uniformly

dispersed in liquid vehicle

To ensure dose to dose content uniformity

Penetrability of particles

Inhaled for deposition deep in the respiratory

tract

Example: 1 to 5 um

Range: 0.2 to 500 micrometers

Laser holography

Particles individually imaged and sized

Pulsed laser fired through an aerolized particle

spray and photographed in 3 dimensions
(holographic camera)

Range: 1.4 to 100 micrometers

Cascade impaction

Principle: a particle driven by an air stream

will heat a surface in its path but its inertia is
sufficient to overcome the drag force that tends
to keep it in the airstream

Particles separated into various size ranges by

increasing the velocity of the airstream

Driven by an airstream will hit a surface in its

path, provided that its inertia is sufficient to
overcome the drag force that tends to keep in
the airstreams

A single method may be sufficient.

Combination of methods preferred for certainty of size

and shape parameters

Particle reduction points out: a decrease in particle size

will result in an increase in the number of particles and
total surface area (inversely proportional)

In dermal ointments, creams, and ophthalmic

preparations

Examples: fine powders may be 50-100 um in

size

Comminution of Drugs

Sedimentation Rate
Particle size is determined by measuring the terminal
setting velocity of particles through a liquid medium a
gravitational and centrifugal environment

Range: 0.8 to 300 micrometers

Calculated using the Stokes Law

Methods for the Determination of Particle Size

Nongrittiness of solid particles

The Laser, Optics and Holography Rings

Reduction in light reaching the sensor as the

particle dispersed in a liquid or gas, passes
through the sensing zone

Example: fine dispersions have particles

approximately 0.5 to 10 um

Uniform distribution of a drug substance in a powder

mixture or solid dosage form

Light energy diffraction or light scattering

Pulverization by intervention

Reduction of particle size with the aid of a

second agent that can be readily removed from
the pulverized product

Example: camphor readily triturated with a few

drops of alcohol or other volatile solvent (The
pulverized camphor is readily recovered as the
solvent evaporates.)

Levigation

Separate fine particles from coarse by grinding

in water

Reducing particle size forming a paste of the

solid with a minimum amount of a levigating
agent and then triturating the paste in a mortar
or on slab with a spatula

Small-scale preparation of ointments

Reduce the particle size and grittiness of added

powders

Mortar and pestle or ointment tile is used.

Trituration and levigating agent: insoluble

powder (mineral oil and glycerine)

The basis of choice of levigating agent:

Ability to form a smooth paste with

the substance

Compatibility with the product

*** Water cannot be used for

levigating a substance for oleaginous
ointment base.

Comminution of Drugs on a Large-Scale

Various types of mills and pulverizers

Example: FitzMill Comminutor

Used for particle reduction with

attached containment system for
protection of environment and
prevention of product combination

Collection or containment system:

Protects the environment form chemical dust

Reduces product loss

Prevents product contamination

Indicated when the potent and other

ingredients are:
o Same color
o Visible sign of mixing is
lacking
Examples: strychnine sulfate, arsenic, mercury
bichloride,
atropine
in
convenient
concentration using lactose as the diluents for
use at the Rx counter

Sifting

Powders mixed by passing through the sifters:

results in light, fluffy product
Not acceptable for incorporation of potent
drugs into a diluent powder

Tumbling (rotating chamber)

Use of machine or motorized equipment for
industrial purposes
Time consuming
Small
scale
preparations:
spatulation,
trituration, sifting
Twin Shell Blender

Mixes solid particles

Blending of Powders

The V blender: an efficient and versatile blending

machine for mixing and lubrication process of dry
powders homogeneously

The ribbon blender: an efficient and versatile blending

machine for mixing dry granules and powders
homogeneously
Routes in Administering Medicated Powders

For internal use:

Taken orally after mixing with water
For constitution with a liquid solvent or vehicle
Some inhaled for local and systemic effects
Others as injection
Others as vaginal douche

For external use:

Dusted on the affected area (sifter-type
container) or applied from powder aerosol
Should bear a label marked external use only
or a similar label

Mixing or Blending Powders

Spatulation
Movement of spatula on a sheet of paper or
ointment tile
Not suitable for large quantities of powders or
powders containing potent substances
Suited to mixing solid substances that form
eutectic mixtures (or liquefy when in close and
prolonged contact with one another)
Examples that form eutectic mixtures when
combined: phenol, thymol, camphor, aspirin,
menthol, phenyl salicylate and other similar
chemicals

Trituration
To comminute and to mix powders
Geometric dilution method

Used when a small amount of potent

substance is mixed with a large
amount of diluents

Ensure the uniform distribution of

the potent drug

For oral use has:

Local effects (ex. laxatives)
Systemic effects (ex. analgesic)

Faster rate of dissolution and

absorption (immediate contact with
gastric fluids)
Preferred than tablets and capsules by patients
who have difficulty in swallowing solid dosage
forms
Administered as powders

Doses of some drugs are too bulky

(cant be made into a capsule or
tablet of convenient size)
Medicated Powders

Advantages:
Faster rate of dissolution and absorption
Ease in compounding
For eutectic mixtures

Disadvantages:
Cant mask undesirable taste
Inconvenient to carry
Inaccuracy in dose
Aerosol Powders

Administered by inhalation with the aid of dry-powder

inhalers

Deliver micronized particles of medication in metered

quantities 1um to 6um range in diameter

Treatment of asthma and other bronchial disorders

Contain inert propellants and pharmaceutical diluents

such as crystalline alpha-lactose monohydrate
To aid the formulations flow properties and
metering uniformity
To protect the powder from humidity

Mechanical devices used: pressurized aerosols, spinhaler

(cromolyn Na from capsules), blowers or insufflators
Powders to various parts of the body after
depression of rubber bulb causing turbulence in
the vessel forcing the powder out through the
orifice in the tip
Insufflator

Powder is placed in the vessel.

When the rubber bulb is depressed, internal turbulence

disperses the powder and forces it from orifice.
Insufflations

Finely divided powders introduced into the body cavities

such as the ears, nose, throat, tooth sockets and vagina

Examples:
Norisodrine Sulfate Aerohaler Cartridge
(Abbott): specialized equipment or inhalation
Cromolyn Sodium Powder: relieve bronchial
asthma
Types of Powders

Bulk powders
Dispensing powder medication in bulk
quantities (nonpotent substances)
Bulk powders available in prepackaged
amounts:

Anatacids (ex. sodium bicarbonate)

and
laxatives
(ex.
Psyllium:
Metamucil)
o Taken by mixing with water or
other
beverage
before
swallowing

Douche powders (ex. Massengil

Powder): dissolved in warm water by
the patient for vaginal use

Mediacated topical anti-infectives:

for external application to the skin
(ex. bacitracin zinc and polymyxin B
sulfate) or antifungals (ex. tolnaftate)

Non-medicated: Brewers yeast

powder
containing
B-complex
vitamins and other nutritional
supplements

Divided Powders
Form of individual dosing units (block
and divide method)
Dispensed in chartulae (folded papers),
metal foil, small heat-sealed or resealable
plastic bags
Based on the amount to be taken or used
at a single time
Examples: headache powders, powdered
laxatives, and douche powders
Properly blended using the geometric
dilution method for potent substances
Block and divide method

For nonpotent powders

Entire amount of prepared powder on

a pill tile

With a large spatula divided into

equal amounts
Forms
rectangular
or
square block of powder
Having uniform depth

Each block transferred to a powder

paper and wrapped
Geometric dilution method

Powders properly blended

Small amount of potent substances

mixed with large amount of diluents

Ensures uniform distribution of the

potent drug (same color with other
ingredients and visible sign of
mixing is lacking)
No powder in the folds, and should not
escape with moderate agitation
Label placed on the container or affix a
label of directions to each paper
Cellophane or plastic envelopes (moisture
resistant resulting in uniform packaging)

To enclose individual doses or units

Used than folded individual powder

papers
Advantages of divided powders:

Flexibility

Rapid therapeutic effect

Stability

Ease of administration
Disadvantages of divided powders:

Time consuming to prepare

Not well suited for dispensing of

many unpleasant tasting hygroscopic
drug

Inaccuracy
o

Papers that may be used

Simple bond paper: opaque paper

with no moisture resistant properties

Vegetable
parchment:
opaque
moisture resistant

Glassine: glazed transparent moisture

resistant

Waxed paper: transparent waterproof

paper
Powders containing:

Hygroscopic
and
deliquescent
materials: waterproof or waxed paper

Limited barrier against moisture is

necessary: glassine and vegetable
parchment papers

Volatile components: waxed or

glassine papers

Neither volatile nor ingredients

adversely affected by air moisture:
white bond paper
Examples of finely divided powders:

Oral powders: supplied as finely as

divided powders or effervescent
granules

Douche powders: generally dissolved

in warm water for vaginal use
Medicated
or
non-medicated
powders: for external application
usually dispensed in sifter cans for
convenient application the skin
Dentifrices or dental cleansing
powders
Denture powders: for dentifrices or
foe adhesive to hold dentures

Douche Powders

Products completely soluble and are intended to be

dissolved in water prior to use as antiseptic or cleansing
agent for body cavity

Components:
Boric acid or borax
Astringents as K alum, ammonium alum,
ZnSO4
Antimicrobial as oxyquinoline sulfate or
povidone iodine
Quaternary ammonium
compounds
as
benzethonium chloride
Detergents as sodium lauryl sulfate
Oxidizing agents as sodium perborate
Salts as sodium citrate, sodium chloride
Aromatic as menthol, thymol, eucalyptol,
methyl salicylate and phenol

Packaging: may be in a wide mouth glass jar to protect

from volatile constituents and by bulk powder boxes
Dentifrices

Form of bulk powder, generally containing flavors, soap

or detergent, mild abrasive and a polishing agent
Forms: paste, powder, liquid, and block and solid
Use: with a tooth brush for the purpose of cleansing the
accessible surfaces of the teeth
Composition: abrasives such as calcium carbonate,
calcium phosphate, calcium sulfate, insoluble sodium
metaphosphate, hydrated Al2O3, MgCO3, and phosphates,
NaHCO3, and NaCl
Dentifrices contain non-carbohydrates sweetening agents
but a few contain sugar

Dusting Powders

Non-toxic preparations for local application and

therefore no systemic effect
Dispensing: should be dispensed in a very fine state of
subdivision to enhance effectiveness and minimized
irritation
Packaging: available in sifter type containers or pressure
aerosols, the latter more expensive but protects from air,
moisture and contamination
Uses: lubricants, absorbents, antiseptics, antipruritics,
astringents, and antiperspirant
Official powdered vegetable drugs:
Powdered Belladona Extract NF
Powdered Digitalis Extract
Powdered Ipecac USP
Powdered Opium USP
Powdered Rauwolfia Serpentina NF
Official powders:
Ampicillin Soluble Powder: dry mixture of the
ampicillin and diluents and stabilizing
Polymixin B Sulfate and Bacitracin Zinc Topical
Powder, USP: used as a topical anti-infective

Compound Cloquinol Powder, USP: mixture of

cloquinol lactic acid, zinc stearate and lactose
vaginal insufflations as an anti-chomonal
Nystatin Topical Powder USP: employed as a
topical dusting powder in the treatment of the
mycotic infections
Tolnaftate Powder USP: treatment of fungal
infection
Official powders for topical use:
Absorbable Dusting Powder: gloves lubricants
Compound Iodochlorohydroxyquin Powder, NF:
vaginal insufflations as antimicrobial
Methylbenzenthonium Chloride Powders, NF: local
anti-infectives for diaper rash in infants

Granules

Prepared aggromalates of smaller particles of powder

Irregularly shaped but may be spherical

4-12 sieve size range, although granules of various mesh

sizes may be prepared depending upon their application

Provide a pleasant vehicle for selected drug products

with bitter, salty taste

Prepared by: wet method, dry method

Examples:
Pricipen (ampicillin): for oral suspension (for
reconstitution)
Senokot granules: for laxative
Effervescent products as Bromo Seltzer
K-Lyte: granulations of effervescent products
compressed into tablet

Preparation of granules:
Wet Method:

One basic wet method

o Moisten the powder or powder
mixture
o Pass the paste through a
screen of the mesh size (to
produce the desired size of
granules)
o Granules are placed on
drying trays and dried by
air or under heat. Granules
periodically moved on the
drying trays to prevent
adhesion into a large mass.

Another type of wet method

Fluid bed process: particles

in a conical shaped
equipment dispersed and
suspended; liquid excipient
sprayed and the product
dried

Granules or pellets of
defined
particle
size
formed
Dry Granulation Method

Dry method or fusion method:

material passed through a roll
compactor then through a granulating
machine
Also called slugging: compression of
powder or a powder mixture under
8000-12000 pounds of pressure
(depending on physical properties of
powder)
Increases particle density and
improves powder flow
Milling equipment: used to improve
flow, reduce segregation, enhance
drying, and limit wide particle size
distribution
granules which are advantageous over

Characteristics of
powders:
Flow well
More stable to atmospheric humidity
Less likely to cake or harden upon standing
Easily wetted by liquids
Effervescent granulated salts
Granules or coarse to very course powders
containing a medicinal agent in a dry mixture
Composition: sodium bicarbonate, citric acid,
tartaric acid
If water is added: effervescence
If tartaric only: loose firm
If citric only: pasty
Pleasant vehicle to mask of bitter and salty
tastes
Example: sodium phosphate: cathartic
Two methods of preparation:

Dry method or fusion method:

binding agent for the powder
mixture: one molecule or water

present in each molecule of citric

acid

Wet method: binding agent: water

added to alcohol as the moistening
agent not the water of crystallization
from the citric acid: forming the
pliable mass for granulation
o Examples:
Zantac
Efferdose tablets
o Lactinex granules: mixed
culture of Lactobacillus
acidophilus
and
Lactobacillus bulgaricus in
1g packets
o Treatment
of
uncomplicated
diarrhea,
usually mixed with water,
beverages, sprinkled on
food or eaten plain
Dry and wet methods:

Objectives of using the method:

o To determine the proper
formula for the preparation
that will result in effective
effervescent and effect of
the product
o Efficient use of the acids
and base present
o Stable granulation
o Pleasant taste