Aira Jhamaica Dimacale  Made of wire cloth woven (not coated or

plated) from brass, bronze, and other suitable

Pharmaceutical Dosage wire

Chapter 6: Powders and Granules  Granules

Powders  Prepared agglomerates of powdered particles

 Intimate mixtures of dry, finely divided drugs and/or  Contain one or more active ingredients with or
chemicals used externally or internally without other ingredients

 Medicated powder:  4-12 sieve size range

 Internal use: oral powder  Granulations of powders used in tablet making

(12-20 sieve range)
 External use: topical powder
Opening of Standard Sieves
Uses of Medicated Powders in Therapeutics
Sieve Number Sieve Opening Sieve Number Sieve Opening
 To fabricate solid dosage forms as tablets and capsule
2.0 9.50 um 70.0 212.00 um
 Blended with powdered fillers and other
pharmaceutical ingredients 3.5 5.60 um 80.0 180.00 um

 To make various liquid dosage forms 4.0 4.75 um 100.0 150.00 um

 Dissolved or suspended in solvents or liquid 8.0 2.36 um 120.0 125.00 um

vehicles
10.0 2.00 um 200.0 75.00 um
 To prepare medicated ointments and creams
20.0 850.00 um 230.0 63.00 um
 Incorporated into semisolid bases
30.0 600.00 um 270.0 53.00 um
Medicated Powders
40.0 425.00 um 325.0 45.00 um
 Internal use:
50.0 300.00 um 400.0 38.00 um
 Taken orally after mixing with water
60.0 350.00 um
 Some are inhaled for local effects (laxatives) or
systemic effect (analgesic)

 External use: Particle Size and Analysis

 Dusted on the affected area from sifter-type  Particles of pharmaceutical powders range from:
container or applied from powder aerosol
 Extremely coarse: about 10 mm to 1 cm in
 Should bear a label marked external use only diameter
Solid Materials  Extremely fine: approaching colloidal
dimensions of 1 micron or less
 Characterized to determine their chemical and physical
features before the preparation of pharmaceutical  Micromeritics
products including:
 Science of small particles
 Morphology, purity, solubility, stability,
particle size, uniformity, compatibility with  Characteristics included: particle size, angle of
any other formulation components repose, bulk volume, size distribution,
porosity, apparent density, shape, true volume,
 For efficient production of a finished dosage form: bulkiness
optimum therapeutic efficacy, adjustment and control of
powder’s particle size USP Standings for Powders of Animals and Vegetable Drugs

Definition of Some Terms USP Descriptive Sieve Size: All Fineness

Terms Particles Pass
 Sieves Through

 For pharmaceutical testing and measurement, Very Coarse (No. 8) 8 Not more than
reduction of particle size of powders (nmt) 20% through

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 a no.60 sieve Methods for the Determination of Particle Size

Coarse (No.20) 20 Nmt 40% through a  Light energy diffraction or light scattering
no.80 sieve
 Reduction in light reaching the sensor as the
Moderately Coarse 40 Nmt 40% through a particle dispersed in a liquid or gas, passes
(No.40) no.80 sieve through the sensing zone

Fine (No.60) 60 Nmt 40% through a  Range: 0.2 to 500 micrometers

no.100 sieve
 Laser holography
Very Fine (No.80) 80 No limit to greater
fineness  Particles individually imaged and sized

 Pulsed laser fired through an aerolized particle

spray and photographed in 3 dimensions
Purpose of Particle Size Analysis in Pharmacy (holographic camera)

 To obtain quantitative data of drug and other components  Range: 1.4 to 100 micrometers
used in pharmaceutical formulations on the size,
distribution, and shape  Cascade impaction

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
 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
 To ensure dose to dose content uniformity
 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)

 Penetrability of particles

 Inhaled for deposition deep in the respiratory

tract

 Example: 1 to 5 um

 Nongrittiness of solid particles

 In dermal ointments, creams, and ophthalmic

preparations Comminution of Drugs

 Examples: fine powders may be 50-100 um in  Pulverization by intervention

size
 Reduction of particle size with the aid of a
The Laser, Optics and Holography Rings second agent that can be readily removed from
the pulverized product
Sedimentation Rate
 Example: camphor readily triturated with a few
 Particle size is determined by measuring the terminal drops of alcohol or other volatile solvent (The
setting velocity of particles through a liquid medium a pulverized camphor is readily recovered as the
gravitational and centrifugal environment solvent evaporates.)

 Range: 0.8 to 300 micrometers  Levigation

 Calculated using the Stoke’s Law

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  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
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
 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
 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
(can’t 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:
 Can’t mask undesirable taste
 Inconvenient to carry
 Inaccuracy in dose
Aerosol Powders
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  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 formulation’s 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: Brewer’s 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
o 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
 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
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  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
 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

 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  Preparation of granules:
metaphosphate, hydrated Al2O3, MgCO3, and phosphates,  Wet Method:
NaHCO3, and NaCl  One basic wet method
 Dentifrices contain non-carbohydrates sweetening agents o Moisten the powder or powder
but a few contain sugar mixture
o Pass the paste through a
Dusting Powders screen of the mesh size (to
produce the desired size of
 Non-toxic preparations for local application and granules)
therefore no systemic effect o Granules are placed on
 Dispensing: should be dispensed in a very fine state of drying trays and dried by
subdivision to enhance effectiveness and minimized air or under heat. Granules
irritation periodically moved on the
 Packaging: available in sifter type containers or pressure drying trays to prevent
aerosols, the latter more expensive but protects from air, adhesion into a large mass.
moisture and contamination  Another type of wet method
 Uses: lubricants, absorbents, antiseptics, antipruritics,  Fluid bed process: particles
astringents, and antiperspirant in a conical shaped
 Official powdered vegetable drugs: equipment dispersed and
 Powdered Belladona Extract NF suspended; liquid excipient
 Powdered Digitalis Extract sprayed and the product
 Powdered Ipecac USP dried
 Powdered Opium USP  Granules or pellets of
 Powdered Rauwolfia Serpentina NF defined particle size
 Official powders: formed
 Ampicillin Soluble Powder: dry mixture of the  Dry Granulation Method
ampicillin and diluents and stabilizing  Dry method or fusion method:
 Polymixin B Sulfate and Bacitracin Zinc Topical material passed through a roll
Powder, USP: used as a topical anti-infective compactor then through a granulating
 Compound Cloquinol Powder, USP: mixture of machine
cloquinol lactic acid, zinc stearate and lactose  Also called slugging: compression of
vaginal insufflations as an anti-chomonal powder or a powder mixture under
 Nystatin Topical Powder USP: employed as a 8000-12000 pounds of pressure
topical dusting powder in the treatment of the (depending on physical properties of
mycotic infections powder)
 Tolnaftate Powder USP: treatment of fungal  Increases particle density and
infection improves powder flow

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  Milling equipment: used to improve
flow, reduce segregation, enhance
drying, and limit wide particle size
distribution
 Characteristics of granules which are advantageous over
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