Introduction to Powders
and Granules
Contents
• Powders
– advantages, disadvantages, classification
• Blending
of Powders
• Divided powders
• Bulk internal powders
• Cachets
• Seidlitz
powders
• Granules,
need for granules
• Reconstituted
Granules
• Effervescent
Granules
• Methods
of Preparation of effervescent granules
• Dispensing
of Powders involving Special Problems.
• Volatile
Substance
• Hygroscopic
And Deliquescent Powders
• Efflorescent
Powders
• Eutectic
Mixtures
• Liquids
• Explosive
Powders
• Potent
Drugs
Learning objectives
At the end
of this lecture, student will be able to:
– Define
the term powders and granules
– List
the advantages and disadvantages of powder dosage form
– Classify
powders
– Give
appropriate examples for various classes of powders
– List
the methods for blending of powders
– Explain
the methods used for blending of powders
– Explain
bulk powders for internal use
– Explain
cachets and types of cachets
– Discuss
preparation of cachets
– Explain
seidlitz powder
– Explain
the significance of granules
– List
the advantages of granules as solid dosage form
– Explain
effervescent granules
– Explain
methods of preparation of effervescent granules
– Explain
powders having dispensing problems
– Indicate
the remedial measures for packing such special powders
Powders
q A
powder is a homogeneous mixture
q More
or less finely divided drugs or chemicals in dry form
q May
be intended for internal (oral powders) or external (topical powders) use
q Pharmaceutical
powders à size
between 0.1 and 10µ
q Constituted powders
Advantages
q Physically
and chemically more stable when compared to liquid dosage form Eg: Does not
undergo hydrolysis
q Insoluble medicaments and those
susceptible to microbial attack can be dispensed in powder dosage form
q Easy
drug administration for very large dose of drugs Eg: Indigestion,
constipation, diarrhea
q It
is well accepted by pediatric and geriatric patients Eg: Small children
have difficulty in swallowing tablets and capsules, powders can overcome this
difficulty with instructions to mix them with a sweet substance such as syrup,
honey or jam
q The rate of dissolution and absorption is
faster in powder dosage form when compared to any other solid dosage forms
Disadvantages
q Bulk
dosage forms cause difficulty in handling and transport
q They
are not easily transferrable from a container and may spill
q In
bulk dosage forms, medicaments often have same weight but different volumes and
hence this method is inaccurate and therefore potent substances should not be
dispensed in bulk powders
q The
method of preparation and packaging are time consuming
q Drug
substances that are having an unpleasant taste are not suitable to administer
in powder form
q The
substances that are hygroscopic, deliquescent, volatile and oxygen sensitive
are not suitable to be administered in powder form
Classification of Powders
q According
to division of prescribed dose
– Divided
powders
– Bulk
powders for internal use
– Bulk
powders for external use
– Effervescent
powders/ Granules
– Powders
enclosed within an edible shell (like cachets and capsules)
q According
to composition
– Simple
powders
– Compound
powders
Divided Powders / Single Dose Powders
q Divided
powders are unit dose powders
q Packed in properly folded papers and dispensed
in envelops, metal foil, small heat sealed plastic bags or other containers
q The
number of active ingredients may be one (Simple powders) or more than one
(Compound powders)
q Manipulative losses are inevitable; therefore
it is necessary to prepare for atleast one powder packet extra to requirement
Preparation of Divided Powders
Step 1. The ingredients are weighed correctly
Step 2. Blended by geometric dilution in ascending order of
weights
Step 3. Mixture is then either divided into blocks of equal
size (dose) or
Step 4. Packed in paper which is folded according to the pharmaceutical
art
Step 5. Placed in envelope or powder box and dispensed
Colourless Powders
Step 1. If all the materials present in the powders are
white in color
Step 2. Add a drop amaranth alcoholic solution to the
powders and mix it
Step 3. The end point of mixing would be even spreading of
the pink colour of amaranth
Mixing of Powders
q When
two or more powdered substances are to be combined to form a uniform mixture
q It
is best to reduce the particle size of each powder individually before weighing
and blending
q Depending
on
– The nature of the ingredients
–
The amount of powder to prepare
–
The equipment available, powders may be blended
by
q Spatulation
q Trituration
q Sifting
q Tumbling
Spatulation
q The
blending of powders with a spatula on a tile or paper used for small
quantities
q Used
when the mortar and pestle technique is undesirable
q The
method is not suitable for large quantities of powders
q The
method is not suitable for powders containing one or more potent substance
q because homogenous blending is not certain
q There
is no particle size reduction, so the powders to be mixed must be fine and of
uniform size
q Because
no pressure is used, the resulting powder is usually light and is not compacted
q This
method should be used when hard trituration is to be avoided, such as when
blending powders that liquefies on trituration
q Eg:
phenol, camphor, menthol, thymol, aspirin, phenyl salicylate etc.
Trituration
q Trituration
Applied both to comminute and to mix powders
q When
a small amount of a potent substance is to be mixed with a large amount of
diluent, The geometric dilution method is used to ensure the uniform
distribution of the potent drug
q When
the potent and non-potent ingredients are of the same color and a visible sign
of mixing is lacking, trituration is preferred
Geometric Dilution Method
Step 1. Equal volume of potent drug + dilulent in a mortar
Step 2. Mixed thoroughly by trituration
Step 3. A second portion of diluent equal in volume to the mixture
is added
Step 4. The trituration is repeated
Step 5. Process is continued by adding equal volumes of
diluent to the powder mixture and repeating until all of the diluent is
incorporated
q If
100mg of potent drug is required to be mixed with 900mg lactose,
100mg of drug
+ 100mg of lactose =
200mg mixture
200mg of mixture
+ 200mg of lactose =
400mg mixture
400mg of mixture +
400mg of lactose = 800mg mixture
800mg of mixture +
remaining mg of lactose = 1000mg mixture
Sifting
q Powders
may also be mixed by passing them through sifters
q Sifting results in light fluffy product
q The
process is not acceptable for incorporation of potent drugs into a diluent
powder
Tumbling
q Tumbling
of the powders are carried out in an enclosed rotating chamber / container
q Special
small scale and large scale motorized powder blenders have been developed which
mix powder by tumbling motion
q Mixing
by this process is time – consuming
Eg:
Twin shell blender
Divided Powders
q
If the powder
contains a potent medicine, Then dilute them with a suitable diluent ,In the
case of codeine phosphate we dilute them with lactose to bring them enough
weight.
q
If a powder is
hygroscopic in nature, the final powder is double wrapped.
q
If a powder
contains materials are eutectic mixture, The eutectic formation is allowed,
Absorbed onto a diluents, The final powder is double wrapped.
q
If a powder
contains an effervescent mixture, The acid and the alkaline salts are separately
packed, Dispensed with suitable directions.
q
After a powder
has been properly blended (using the geometric dilution method for potent
substances)
q
It may be divided into individual dosing units
based on the amount to be taken or used at a single time
q
Each divided
portion of powder may be placed on a small piece of paper that is folded to
enclose the medication
q
A number of
commercially prepared premeasured products are available in folded papers or
packets, including headache powders, powdered laxatives, and douche powders
Bulk Internal Powders
q
Bulk powders are
usually a simple mixture of the prescribed medicament without additional
ingredients
q
It is preferable
to administer large quantities with food or drinks
q
Fine particles
dissolve quickly and the onset of action can be seen rapidly
q
The powders for
internal use are sometimes converted into granules of desired size
q
The main
additives needed for powders are
q
diluents like
lactose, sucrose, sorbitol, micro crystalline cellulose (MCC)
q
organoleptic
additives like flavoring and sweetening agents are must while colors may or may
not be used
q
Bulk powders
contain many doses in a wide mouth container i.e., suitable to remove the
powder by a teaspoon
q
The non-potent
and light/ bulky powders are used in bulk powder form
q
Examples :
q
Antacid,
laxative, purgative etc.,
q
Eg: Rhubarb
powder, light magnesium carbonate, heavy magnesium carbonate, ginger powder
etc.,
Compound Magnesium
Trisilicate Oral Powder BP
q
Contains
– Magnesium tricilicate
– Chalk in powder
– Sodium bicarbonate
– Heavy magnesium carbonate
q
Procedure
–
The powders are
mixed in a mortar in order of increasing bulk volume
–
Pass the
resulting mix through a 250µm sieve
–
Lightly mix and
pack
q
Storage and
container-
In an amber color glass screw capped bottle in a dry
place
q
Directions
The powder should be taken mixed with a little water
or other fluid between meals
q
Uses-
Adsorbent
Antacid for the treatment of dyspepsia
Cachets
q
Solid unit dosage
forms of the medicament
q
The drug is
enclosed in a tasteless sheet made by pouring a mixture of rice flour and water
q
The water
evaporates and a sheet of wafer is formed
q
They are also
known as wafer capsules or capsula amyacea
q
Cachets are used
to enclose nauseous powders and can hold 0.2 to 1.5 g of powders
q
Cachets are hard
to swallow
q
Before
administration the cachets should be dipped in water for a few seconds
q
Then placed on
the tongue and swallowed with the help of water.
q
After swallowing,
the cachet will disintegrate and the powder will be released.
Advantages
q
Can be made with
simple machinery.
q
Large doses of
drugs can be enclosed in cachets.
q
Large sizes of
cachets are easy to swallow once they have been softened by immersion in water.
q
Disintegrate quickly in the stomach.
q
Nauseous drugs
and those with an unpleasant taste can be dispensed.
Disadvantage
q
Easily damaged
q
Give poor
protection from light and moisture
q
Must be softened
before swallowing
q
Occupy more space
than capsule and tablet strips
q
Not very suitable
for filling by large scale machinery
Types of Cachets
q
There are two
types of cachets
q
Wet seal cachets
q
Dry seal cachets
Wet Seal Cachets
q
These are sealed
by moistening the edges with water
q
They are made up
of two similar halves having flat edges
q
Preparation-
Step 1. The weighed amount of
powder is placed in one half
Step 2. the edges of the other
half is moistened with water
Step 3. moistened half is placed
exactly over the 1st half containing the powder
Step 4. The flat edges of both
the halves are pressed together
Step 5. A perfect seal and powder
is completely enclosed
Cachet Mould
• The standard cachet machine consisted of three metal
plates
• Drilled with holes of different diameter for the size
of the cachet used.
• The first half of the cachet was then fitted in the
base plate.
• The centre plate was then used to mask the rims of the
cachets to prevent powder deposit.
Preparation of Cachets
q
Funnels were then
used to deposit an appropriate dose of the powdered drug into the lower part of
the cachet
q
When the cachets
were filled, moisture was applied to the rims of the cachet halves in the top
plate
q
The centre plate
was then removed and the two cachet halves brought together
q
After a few
minutes the cachets were dry and could be removed
Dry Seal Cachets
q
They do not
require moisture for sealing
q
They consists of
2 halves the upper half and the lower half
q
Labelling
Immerse in water for few seconds and
then swallow with the help of water
q
Preparation
Step 1. They consists of 2 halves
the upper half and the lower half
Step 2. The diameter of the upper
half is slightly larger than the lower one
Step 3. The powdered drug is
filled in the lower half and the upper half is fitted over the lower half
Step 4. The filled cachets are
then sealed in a machine by pressing the two halves, removed and packed
Seidlitz Powder
(Compound Effervescent Powder)
q
Seidlitz powders
are administered as effervescent draught
q
It consists of
two powders
q
Powder No. 1 (both
wrapped in blue paper)
Sodium potassium tartrate
Sodium bicarbonate
q
Powder No. 2 (wrapped
in white paper)
Tartaric acid
Seidlitz Powder –
Directions
q
The contents of
the blue paper are dissolved in a tumblerful of cold or warm water, the
contents of the whitepaper are added, the mixture is stirred the product is
taken while effervescing
q
As sodium
bicarbonate and tartaric acid are both hygroscopic at high humidities
q
An inner wrapper
of waxed paper is used
q
This preparation
is slightly acidic due to the excess of tartaric acid
q
Tartaric acid is added to overcome the salty
taste of the preparation
Granules
q
Bulk granules can
be used to deliver bulky medicaments of low potency
q
Granules packed
in individual sachets have accurate dosage and protection from the atmosphere
q
Granules
containing potent substances should not be supplied in bulk because of the risk
of wrong dosage
q
Granulation of a
powder allows addition of flavouring agents and coloring agents
q
Easily handled
q
Attractive
product
Need for Granules
q
Solid medicaments
which are required to be administered orally in large doses can be given as
granules
q
They cannot be
prescribed in tablets and capsules because for a single dose more than one have
to be take
q
Some medicaments
are difficult to dispense as such in powder form because of its bitter,
nauseous and unpleasant taste
q
It is also
difficult to convert it into liquid dosage form due to stability problem
q
The only
alternative is to convert these powdered medicaments into granular form
q
Solid medicaments
are mixed with sweetening, flavouring and colouring agent
Preparation of Granules
q
A suitable
granulating agent is added to moisten the powders so as to make a coherent mass
q
These coherent
mass will be passed through sieve no. 10 or 16 to make granules
q
Granules will be
dried in a hot air oven at a temp not exceeding 60°C
q
The dried
granules are passed through sieve no. 20 or 24 and stored in a dry well closed
wide mouthed bottles
Advantages
q
Free flowing
q
They are more
stable to the effects of atmosphere humidity as their surface area is less than
of powder
q
Less likely to cake or harden upon standing
q
Easily wetted by liquids than certain light
and fluffy powders (which tend to float on the surface)
q
Preferred for dry
powders intended to be constituted into solutions or suspensions
Reconstituted Granules
Drug + suspending,
sweetening, flavouring, colouring and granulating agents
Granules prepared
Packed in bottles
Directions on its label for
reconstitution.
q
A number of
commercial products containing antibiotic drugs that are unstable in aqueous
solution
q
Prepared as small
granules for constitution with purified water before use
Eg: Erythromycin, phenoxy methyl
penicillin, ampicillin
q
Label should
state the time limit within which reconstituted preparation should be used
Effervescent Granules
q
Specially
prepared solid dosage form of medicament, meant for internal use
q
They contain a
medicinal agent in a dry mixture composed of sodium bicarbonate, citric acid
and tartaric acid
q
When added to
water, the acids and the base react to liberate CO2 resulting in
effervescence
q
The resulting
carbonated mixture masks an undesirable taste of any medical agent present
Effervescent Granules Vs
Effervescent Powders
|
Effervescent Granules |
Effervescent Powders |
|
Coarse particles of mixed powder |
Small powder particles |
|
Rate of dissolution less |
Rate of dissolution more |
|
No violent and uncontrollable |
violent and uncontrollable |
q
Sudden and rapid
effervescence could overflow the glass and leave little residual carbonate in
the solution
q
Contains –
A medicinal agent
Sodium bicarbonate
Citric acid
Tartaric acid
Why two acids..?
q
Combination of
two acids avoids certain difficulties
q
When tartaric
acid is used alone, the resulting granules lose their firmness and readily
crumble
q
When Citric acid
used alone results in sticky mixture difficult to granules
Reaction involved in Effervescent Granules
3NaHCO3 + C6H8O7.
H2O —————–à Na3C6H5O7
+ 4 H2O +3CO2 á
Sodium Citric acid
Sodium
Bicarbonate Citrate
2 Na HCO3 + C4H6O6
—————–à Na2C4H4O6 + 2H2O + 2CO2 á
Sodium tartaric acid Sodium
Bicarbonate Tartarate
Methods of Preparation
q
Effervescent
granules are prepared by two general methods
– The dry or fusion method
– The wet method
Fusion Method / The Dry
Method
q
Each molecule of
citric acid contains one molecule of water
Acts as the binding agent for the powder mixture
q
Before mixing the
powders,
The citric acid crystals are powdered
Then mixed with the other powders of the same sieve
size
Gives uniformity of the mixture
q
Sieves and other
mixing equipment should be made of stainless steel or other material resistant
to the effects of the acids
q
The mixing of the
powders is performed rapidly
q
This is to avoid
premature chemical reaction [Which occurs by absorbing moisture from a low
humidity environment]
q
After mixing the
powder is placed on a china dish in an oven at 34-40°C
q
During the
heating process, an acid resistant spatula is used to turn the powder
q
The heat causes
the release of the water of crystallization from the citric acid
q
which in turn
dissolves a portion of the powder mixture setting of the chemical reaction
q
consequent
release of some CO2
q
This causes the
softened mass of powder to become spongy
q
When of the
proper consistency (as bread dough) is formed
q
It is removed
from the oven(heat source) and rubbed through a sieve to produce granules of
the desired size
q
The granules are
dried at a temp not exceeding 54°C and immediately placed in containers
and tightly sealed
Sieve no. #4 —————— large granules
Sieve no. #8 —————— medium
Sieve no. #10 —————— small granules
Wet Method
The source of binding agent
is not the water of crystallization from the citric acid
Alcohol is added to moisten the anhydrous powders and
helps them to form a pliable (flexible) mass for granulation
Just enough liquid is added
to prepare a mass of proper consistency
then granules are prepared
and dried
Special Powders
Dispensing of Powders involving Special Problems.
q
Volatile
Substance
q
Hygroscopic And
Deliquescent Powders
q
Efflorescent
Powders
q
Eutectic Mixtures
q
Liquids
q
Explosive Powders
q
Potent Drugs
Volatile Substance
q
Certain vegetable
powders contain volatile oils.
q
To prevent the
loss of volatile oils, these vegetable drugs must be powdered lightly in a
mortar.
q
Volatization of
substances like menthol, camphor and essential oils may take place on incorporation
in powders.
Volatile Substance –
Dispensing Remedies
q
This is prevented
or minimized by the use of double wrapping.
q
The inner wrapper
should be wax paper
q
Outer wrapper may be of any thick paper.
Hygroscopic and Deliquescent Powders
q
The powders which
absorb moisture from the atmosphere are called hygroscopic powders
q
Certain powders absorbs moisture to such a
great extent that they go into solutions form and are called as deliquescent
powders.
q
Calcium chloride,
potassium acetate, iron, ammonium chloride, ammonium citrate, pepsin,
phenobaritone, sodium bromide, sodium iodide, potassium citrate, zinc chloride
etc.
Hygroscopic and Deliquescent Powders -Dispensing
Remedy
q
Such substances
are supplied in granular form
Ø
Expose less
surface area to the atmosphere.
q
These powders
should not be very finely divided
q
Should be double
wrapped.
q
Further wrapping
in aluminium foil or plastic cover.
q
Whether the
tendency of the hygroscopic materials to absorb water can be countered ?
q
Yes…
q
How ?
q
By incorporation
of finely subdivided substances like magnesium oxide, magnesium carbonate,
calcium carbonate, talc, colloidal silica
q
Complete for
moisture and take it up before it can harm the medicament.
Efflorescent Powders
q
Some crystalline
substances liberate water of crystallization wholly or partly…
q
When ??
q
On exposure to
atmosphere or during trituration
q
Thus become wet
or liquefy
q
Eg: caffeine,
citric acid, ferrous sulphate, sodium borate etc.,
Dispensing Remedy
q
This difficulty
may be overcome
q
By using either
corresponding anhydrous salt or an inert substance
q
Which have to be
mixed with efflorescent substances before incorporating with other ingredients.
Eutectic Mixtures
q
When two or more
substances having low melting point are mixed together,
q
they liquefy due
to the formation of a new compound
q
which has a lower
melting point than room temperature.
q Eg: Menthol, thymol, camphor, phenol, salol, aspirin,
phenacetin, chloral hydrate, salicylic acid, phenyl salicylate.
q These substances can be dispensed by two methods
o
Dispense as
separate set of powders with directions that one set of each kind shall be
taken as a dose
o
An equal amount
of any of inert absorbent like magnesium carbonate, light magnesium oxide,
kaolin, starch, lactose, calcium phosphate etc., may be mixed with eutectic
substances and then blended together lightly with a spatula on a sheet of paper
Formula
q
Dispense 50g of
the following insufflations
Menthol
Camphor
Ammonium chloride
Light magnesium carbonate
q
Dispense 50g of
the following Antipruritic preparation
Menthol
Camphor
Light magnesium carbonate
Method of Preparation
Step 1. Separately powder
each ingredient
Step 2. Weigh required
quantity of menthol, camphor and ammonium chloride.
Step 3. Mix them in ascending
order of their weight in a mortar to form a liquid.
Step 4. Add light magnesium
carbonate to make a free flowing powder.
Step 5. Pass through sieve
no. 85 and dispense in air tight container.
Liquids
q In certain prescription, the liquid medicaments are
also incorporated in dispensing powers.
q If the quantity of the liquid is small, It may be
triturated with an equal amount of powder, then the rest of the ingredients are
incorporated in small portions with continuous trituration.
q If the quantity of the liquid is larger, Then an
absorbent must be added.
q Eg: Liquid extracts and tinctures are evaporated to a
syrupy mass.
Lactose/ some
other diluents is mixed
Then continue the evaporation to dryness.
Mix other ingredients or substitute the liquid
extract by a dry extract.
Explosive Powders
When an oxidizing substances
such as potassium chlorate, Mixed with reducing agents such as tannic acid, There are chances of violent explosion which
may lead to serious consequences.
Eg :
Rx
Potassium chlorate
Tannic acid used as gargle
Sucrose
Method of Preparation
Step 1. Powder each
ingredient separately in a mortar
Step 2. Mix them lightly with
other ingredients. OR Powder each ingredient separately
Step 3. Dispense them in
separate powder paper with suitable directions regarding the use.
Eg for oxidizing agents Eg for reducing agents
Potassium chlorate Charcoal
Potassium dichlorate Sulphur
Potassium nitrate Sulphides
Potassium permanganate Tannic acid
Silver nitrate
Potent Drugs
q
The substances
having minimum dose of less than one grain (60 mg) and poisonous
q
A larger response
at low concentrations
q
The potent drug
is triturated with some diluents to make a weighable quantity for each powder
packet (mixed by geometric dilution method).
Eg: codeine phosphate 10mg
Minimum weighable quantity = 120mg.
q A
powder is a homogeneous mixture
q May
be intended for internal (oral powders) or external (topical powders) use
q In
presence of potent drug, diluents should be added
q Trituration,
Sifting, Tumbling are methods for mixing of powders
q Spatulation
for powders which are fine and uniform size
q Trituration
reduces the powder size along with mixing
q Tumbling
of the powders are carried out in an enclosed rotating chamber / container and
suitable for large scale
q Divided
powders are unit dose powders which may or may not contain potent drug.
q Bulk
powders contain many doses in a wide mouth container i.e., suitable to remove
the powder by a teaspoon.
q Cachets
– solid unit dosage forms of the medicament, in which the drug is enclosed in a
tasteless sheet made by pouring a mixture of rice flour and water.
q Seidlitz
powders are administered as effervescent draught.
q Seidlitz
powder
Powder No. 1
Sodium potassium tartrate
Sodium bicarbonate
Powder No. 2
Tartaric acid
q A
number of commercial products containing antibiotic drugs that are unstable in
aqueous solution are dispensed as reconstituted powders
q Effervescent
Granules contain a medicinal agent in a dry mixture composed of sodium
bicarbonate, citric acid and tartaric acid
q Effervescent
Granules can be prepared by wet method or dry method
q In
wet method anhydrous citric acid is used and in dry method hydrated citric acid
is used
q Volatile
substances like menthol, camphor and essential oils may volatilize on
incorporation in powders. Therefore double wrapped.
q The
powders which absorb moisture from the atmosphere are called hygroscopic
powders
q Certain
powders absorbs moisture to such a great extent that they go into solutions
form and are called as deliquescent powders.
q Efflorescent
Powders – on exposure to atmosphere liberate water of crystallization wholly or
partly.
q Eutectic
mixtures – When two or more substances having low melting point are mixed
together, they liquefy due to the formation of a new compound which has a melting point lesser
than room temperature.