Chapter 6
Powders and Granules
Objectives
After reading this chapter, the student will be able to:
1. Differentiate a powder from a granule
2. Explain how a drug's powder particle size influences the
pharmaceutical dosage forms that will be used to administer
it
3. Define micromeritics, the angle of repose, levigation,
spatulation, and trituration
4. Compare and contrast the various types of medicated
powders, for example, bulk, divided
5. Provide examples of medicated powders used in prescription
and nonprescription products
6. Differentiate between the fusion method and wet method for
the preparation of effervescent granulated salts
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Powders
Particle Size and Analysis
Very coarse
#8 sieve
2,360 m
2.36 mm
Coarse
#20 sieve
850 m
0.85mm
Mod. coarse
#40 sieve
425 m
Fine
#60 sieve
250 m
Very fine
#80 sieve
180 m
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Particle Size
Dissolution
Suspendability of suspensions
Uniformity of mixtures in liquids
Penetrability of particles for inhalation
Nongrittiness for ointments, creams, gels
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Particle Size (cont.)
If uniform, will aid in mixing and distribution.
Finer particles may migrate to bottom.
Larger particles may migrate to top.
Differences may change the color intensity of a powder.
Especially important in dermatologicals.
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Comminution of Drugs
Comminution of Drugs
The process of reducing the particle size of a solid
substance to a finer state of subdivision.
Stone mills were the original implement for grinding.
Mortars and pestles are the symbol of pharmacy.
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Objectives of Comminution
Facilitate crude drug extraction
Increase the dissolution rates of drugs
Aid in the formulation process
Enhance absorption
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Methods of Comminution
Manual
Mechanical
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Manual Methods of Comminution
Trituration (to rub to pieces)
Pill tile and spatula
Mortar and pestle
Porcelain
Wedgewood
Glass
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Manual Methods of Comminution (cont.)
Levigation to make smooth
Triturating while moistened with a liquid in which the
powder is insoluble
Pulverization by intervention
Comminution by utilizing a solvent that can be
easily removed
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Mechanical Methods of Comminution
Ball mills
Closed
Continuous
Roller mills
Cutter mills
Hammer mills
Colloid mills
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Mechanical Methods of Comminution
(cont.)
Fluid energy mills
Lyophilization (freeze-drying)
Spray drying
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Blending Powders
When Preparing Dosage Forms
Reduce particle size until uniform with other ingredients.
Start with the substance present in the smallest amount
and add ingredient with next larger quantity (if practical)
using geometric dilution technique. Also tracer method.
Continue adding substances until all are added and
uniformly mixed.
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Blending (Mixing)
A process that tends to result in a randomization of
dissimilar particles within a system
1.
Small-scale blending equipment
Compounding
2.
Large-scale blending equipment
Manufacturing
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Small-Scale Blending Equipment
Pill tile and spatula
Mortar and pestle
Bottle/container
Plastic baggie
Easily cleanable
Dust tight
Provide complete discharge/recovery
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Mixing Mechanisms
Convective mixing
Shear mixing
Diffusive mixing
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Equipment Categories
Batch mixing
Continuous mixing
Tumblers
Double-cone blender
Twin-shell blender
Paddle blenders
Blade and paddle blender
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Factors in Blending
Size
Shape
Density
Electrostatic forces
Limits of blend
Segregation mechanisms
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Medicated Powders
Powder Applications
Dentifrices
Powders used to clean the teeth
Insufflations
Intended for application to the body cavities (e.g.,
tooth sockets, ears, nose, throat, vagina)
Powder aerosols
Antiperspirants, deodorants, feminine hygiene
sprays, body sprays, insufflations, dry lubricants
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Aerosol Powders
Inhalation
Dry-powder inhalers
Micronized powders
External application and nose, throat, lung, and vagina
Insufflators
Powder blowers
Oral inhalation
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Bulk and Divided Powders
Powders: Categories
Bulk powders
Intended to be administered in dosage quantities
that are safe for the patient to measure
Should pass through a 100-mesh sieve
Dusting powders, aerosols, dentifrices, antacids,
laxatives, dietary nutrient supplements, douches
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Dusting Powders
Must be homogenous, free from potential of causing local
irritation
Should flow easily, spread uniformly, and cling to the
skin upon application
Generally dispensed in sifter-top containers
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Powders: Categories
Divided powders (chartula, charts, powder papers,
powders)
Single doses of the powdered drug mixture
individually enclosed in paper, cellophane, or metallic
foil wrappers or packets
Sufficiently potent to require premeasured doses
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Advantages of Divided Powders
1. Allows physicians to prescribe a precise amount of the
drug.
2. More stable than the liquid form of many drugs.
3. Dissolve more rapidly than compressed solid dosage
forms.
4. Rapid dissolution leads to faster blood levels and
possibly less GI irritation.
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Applications
Easily alter dose
Clinical studies, easy to prepare and alter
Infants/young children (sprinkles)
Bulky drugs
Rapid onset of action, good bioavailability
Stable
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Disadvantages of Powders
1. Not suitable for bitter, nauseating, or corrosive drugs
2. Preparation is time consuming, therefore more costly
3. Exposure of powder to atmospheric conditions
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Preparation of Powders
Spatulation
Trituration
Sifting
Tumbling
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Dividing Powder Mixtures into Unit Doses
Weighing each powder
Blocking and dividing
Powder measures
Volumetric template
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Chart Preparation
A chart should fold readily, hold its form, remain clean
with handling, protect contents from atmosphere, be
water-repellant, and present an elegant appearance.
Parchment, glassine, waxed paper
Bond paper
Double wrapping
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Preparation Techniques
Potent drugs
Incorporation of liquids
Volatility
Hydration, crystal hydrates
Hygroscopic and deliquescent powders
Efflorescent powders
Water of imbibition
Eutectic mixtures
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Potent Drugs
Rx
Atropine sulfate
0.4 mg
Mft Pwdr #1, DTD #XII
Sig: i 15 min ac.
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Incorporation of Liquids
Rx
Belladonna tincture
0.6 mL
Acetaminophen
300 mg
M. Disp. Cap. #10
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Incorporation of Liquids (cont.)
Rx
Belladonna extract
Phenobarbital
aa
0.4
Bi subnitrate
24
Kaolin
45
Peppermint oil
0.12
Sig: drams I ac until diarrhea subsides.
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Volatility
Camphor
Iodine
Menthol
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Hydration, Crystal Hydrates
Depending upon the humidity, a salt hydrate may:
Remain unchanged
Deliquesce
Effloresce
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Hygroscopic and Deliquescent Powders
Hygroscopic
Substances that absorb moisture from the air
Deliquescent
Substances that absorb moisture from the air to the
extent that they liquefy by partially or wholly forming
a solution
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Examples: Hygroscopic and Deliquescent
Powders
Ammonium bromide/chloride/iodide
Calcium bromide/chloride
Ephedrine sulfate
Hyoscyamine HBr/sulfate
Lithium bromide
Phenobarbital sodium
Potassium acetate/citrate
Sodium bromide/iodide/nitrate
Physostigmine sulfate/HCl/HBr
Pilocarpine
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Efflorescent Powders
Crystalline substances that become powdery and liberate
their water of crystallization
Alums, atropine sulfate, caffeine, calcium lactate, citric
acid, cocaine, codeine phosphate/sulfate, ferrous sulfate,
morphine acetate, scopolamine HBr, sodium acetate,
sodium carbonate, sodium phosphate, strychnine sulfate,
terpin hydrate
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Water of Imbibition
Colloidal substances may absorb large amounts of water
and retain the appearance of dry powders. This may
cause problems in weighing. The water content varies
with the humidity.
Cellulose, starch, agar, gelatin.
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Eutectic Mixtures
A proportion of components that will give the lowest
melting point
A mixture of components with a melting point less than
room temperature
Aspirin, beta-naphthol, camphor, chloral hydrate,
menthol, phenol, salol, thymol
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Avoiding Eutectics
1. Dispense powders separately.
2. Add an absorbent powder (talc, starch, lactose, calcium
phosphate).
3. Keep ingredients separated as much as possible.
4. Make the eutectic, and then add absorbent to
incorporate the liquid.
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Explosive Mixtures
When triturating an oxidizing agent with a reducing agent
(using a mortar and pestle)
Oxidizing agents
Potassium chlorate/nitrate/permanganate, sodium
peroxide, silver nitrate, silver oxide
Reducing agents
Charcoal, hypophosphites, sulfur, sulfides, tannic
acid, volatile oils
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Dusting Powder (cont.)
Applied to intertriginous areas as a covering to protect
the skin from chafing of friction and moisture
Vehicles: Bentonite, kaolin, kieselguhr, magnesium
carbonate, starch
Note: These vehicles will absorb secretions and dry
the area and impart a cooling effect.
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Dusting Powder (cont.)
The following will impart adhesiveness to the powder:
Aluminum stearate, kaolin, magnesium stearate, zinc
oxide, zinc stearate
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Granules
Granules
Particles ranging from 4 to 10 mesh in size
Not intended for use with potent drugs because of
inherent error when a patient measures the dose with a
teaspoon, scoop, etc.
Good for unstable drugs
Example: antibiotics for reconstitution
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Granule Preparation
Prepared by moistening blended powders and by passing
this mass through a screen or a granulator.
Granules are then air- or oven-dried.
Flavors can be sprayed on the granules and then dried.
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Effervescent Granules
Contain mixtures of citric acid, tartaric acid, or sodium
biphosphate with a bicarbonate and a medicinal agent.
The carbonated solution is a pleasant vehicle and lessens
the bitter and salty taste of salts (e.g., magnesium
sulfate).
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Effervescent Granules (cont.)
Dispense in:
Packets
Wide-mouth bottles
Do not want them to effervesce too quickly as they will
overflow the container during mixing
Examples: Lactinex, Bassoran, Zantac
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Effervescent Granulated Salts
Fusion method
Wet method
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Packaging/Dispensing
Oral administration
Wide-mouth containers
Powder papers
Topical administration
Sifter containers
Puffer units
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Storage/Labeling
Store in dry places.
Protect from light in some cases.
Keep out of reach of children.
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Stability
Dry
USP <795>
6 months if prepared from USP/NF ingredients
25% of expiration date remaining if prepared from
commercial product
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Patient Counseling
Dose measuring technique?
Mix with liquid or food?
Premix and store?
Quantity of powder to apply?
Rub or pat into skin?
Safe to apply where children are playing?
Should the skin be dry? Sweaty?
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