Syllabus: Principles
and Equipment used in the following extraction processes:- Infusion,
Decoction, Expression, Maceration, Percolation.
Extraction:
extraction involves the
separation of medicinally active portions of plant or animal
tissues from the inactive or inert components by using selective
solvents in standard extraction procedures.
Discussion:
Belladonna extract is obtained
from the leaves of the plant Atropa
belladonna. The active ingredient is atropine. Besides atropine starch, lignin,
pigments etc. are also present. So to extract the atropine from the leaves a
selective solvent has to be used so that only atropine is soluble in it. Thus
the active ingredient can be separated from the plant.
Source of drugs (active
ingredients) may be plant or animal.
Plant source: Emetine
from Ipecac root, reserpine from Rauwolfia
serpentina root,
atropine from Belladonna leaves.
Animal source: Cochineal
from insect Coccus cacti.
General procedures:
In this discussion we are
concerned primarily with basic extraction procedures for crude drugs to obtain
the therapeutically desirable portion and eliminate the inert crude material by
treatment with a selective solvent, known as the menstruum.
Let us take some dried leaves
(known as the crude drug) in a
container, add water in it. The active ingredient will come out in the water.
Here water, i.e. the solvent of extraction is called menstruum. Later the water is filtered.
The filtrate is known as the extract.
The damp crude drugs (damp leaves) are called marc. This marc can be expressed i.e., pressed in a chamber
to get the residual liquid, which is mixed with the previous extract.
EXTRACTION PROCESSES |
INFUSION DECOCTION MACERATION PERCOLATION DIGESTION
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Fresh Concentrated
Infusion Infusion
Simple Maceration with Multiple
Maceration adjustment Maceration
Simple Continuous Percolation
Double Triple Percolation Percolation Process for
Maceration Maceration (Soxhlation) Conc. Prepns.
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Reserved Modified
Percolation Percolation
Extraction procedures:
Extraction procedures:
There are several procedures for
extraction: e.g maceration, percolation, digestion, infusion, decoction,
digestion etc. Most pharmacopoeias generally refer to maceration and
percolation for the extraction of active principles from crude drugs.
MACERATION
Principle:
In this process solid ingredients
are placed in a stoppered container with the whole of the solvent and allowed
to stand for a period of at least 3 days (3 - 7 days) with frequent agitation,
until soluble matter is dissolved. The mixture is then strained (through sieves
/ nets), the marc pressed and the combined liquids clarified (cleaned by
filtration) or by decantation, after standing.
N.B.
Stoppered container is generally taken to reduce the
loss of solvents by evaporation. If the volume of solvent is reduced by
evaporation then the extract may become concentrated, which may not be desired.
The drug is allowed to stand for few days
i) to help the solvent to penetrate
the cells of the drugs,
ii) to provide the time for
partitioning the active ingredient into the solvent and
iii) to transfer the drug out of
the cells into the bulk of the solvent.
Frequent agitation is required to reduce the
localized concentration around the cells and tissues.
As indicated in the pharmacopoeia
the process consists of the following:
·
Placing the solid materials with whole menstruum
in the closed vessel and allowed to stand for 7 days shaking occasionally.
·
Strained, pressed the marc and the liquid is
obtained.
·
Liquid (i.e the extract) is clarified by
subsidence or filtration.
The process is normally used for
the preparation of tinctures or extracts and menstruum is usually alcoholic,
hydroalcoholic (in case of tinctures) or may be aqueous.
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1. Simple maceration - a process for
tinctures made from organized drugs e.g. roots, stems, leaves etc.
2. Maceration with adjustment - a process
for tinctures made from unorganized drugs such as oleo-resins and gum resins.
3. Multiple maceration - a process to
prepare concentrated extract. It includes ‘Double maceration’ and ‘Triple
maceration’.
SIMPLE MACERATION
Organized drugs having specific
cell structures like roots, stems, leaves, flowers etc. are extracted by this
procedure.
Apparatus
A wide mouthed bottle or any
other container which can be well stoppered can be used for maceration process.
A closed container is essential to prevent the evaporation of menstruum which
is mostly concentrated alcohol. Otherwise this may lead to variation in
strength as no adjustment in volume is made.
Method
Water or alcohol is used as
menstruum and the drug menstruum ratio is 1 : 10.
·
The drug is placed with the whole of the
menstruum in a closed vessel for seven days. During this period shaking is done
occasionally.
·
After 7 days the liquid is strained and marc is
pressed.
·
The expressed liquid is mixed with strained
liquid.
·
It is then filtered to make a clear liquid.
·
The final
volume is not adjusted.
Explanation
1. Shaking
of the drug during maceration is essential in order to replace the saturated
layers around the drug with fresh menstruum.
2. After
straining, the marc is pressed in a filter press, hydraulic press or hand press
etc. The marc can be squeezed out of a fine muslin piece, when the quantity of
the drug is very small.
3. The
pressed liquid is mixed with the strained liquid and then filtered. No final
adjustment is made, since the volume of pressed liquid is likely to vary with
the process of pressing the marc. If the final adjustment in volume is made, it
will give variation in the concentration of active principle although the
volume of the final preparation may be the same.
4. Filtration
is necessary to remove insoluble cell contents obtained during the pressing of
marc.
Examples: The tinctures made by simple maceration process are-
1. Tincture
of Orange
2. Tincture
of Lemon
3. Tincture
of Squill
MACERATION WITH ADJUSTMENT
The process is used for unorganized drugs.
Apparatus: Same as simple maceration.
Method:
·
In this process the unorganized drug is placed
with 4/5 th of the menstruum in a closed vessel for a period of 2-7 days.
During this period, shaking is done occasionally .
·
After the stated period, the liquid is filtered
and the volume is made up by passing the remaining 1 / 5 the of the menstruum
through the filter.
·
The marc is not pressed.
Explanation
1. The
period of maceration is reduced from 7 to 2 days in some cases, because the
unorganized drugs behave like simple chemicals that dissolve in the solvent
very easily and quickly.
2. 4/5th
of the menstruum is used to keep the drug in contact with it in order to take
into account the increase in volume after dissolving the soluble matter of the
drug. The volume is made up at the end with 1/5th of the menstruum remained.
3. The
marc left is a compact gummy matter. It does not retain the menstruum and hence
it is not necessary to press the marc.
4. The
final volume is made up because all the active constituents of drug get
dissolved in the menstruum. Marc is not pressed. hence, there is no change in
the concentration of the preparation in case the final volume is made up.
Example
1. Tincture
of tolu
2. Compound
tincture of benzoin.
MULTIPLE MACERATION
Multiple maceration process is
carried out in the same way as simple maceration process, but the menstruum
used is divided into two parts in double maceration process and three parts in
triple maceration process
Double maceration process:
In this process, the drug is
macerated twice by using the menstruum which is divided into two parts in such
a manner that the same volume is used for each maceration. The quantity of
menstruum required for two macerations are calculated as follows:
Volume of menstruum required for
first maceration
Total vol. of menstruum - Vol. to be retained by the
drug
= + Vol. to be retained
2
Volume of menstruum required for
second maceration
=
Total vol. of menstruum - Vol. of menstruum
used in first maceration
The volume of menstruum to be
retained by the drug is determined by experiment, in a test batch of drug by
adding a known volume of menstruum to known weight of the drug. After
maceration, straining and pressing of the marc, measured volume volume of
liquid is obtained. Difference in the volume and the volume used represents the
volume retained by the weighable quantity of the drug used.
·
In double maceration process, the whole of the
drug is macerated for 48 hours with the quantity of the menstruum required for
first maceration.
·
The liquid is strained and the marc is pressed.
·
The marc is macerated again for 24 hours with
the remaining menstruum required for second maceration.
·
The liquid is strained and and the marc is
pressed.
·
First and the second liquid is mixed and allowed
to stand for 14 days and then filter.
Examples:
The following concentrated
infusions are prepared by double maceration process:
1. Concentrated
infusion of orange.
2. Concentrated
compound infusion of chirata.
3. Concentrated
compound infusion of gentian.
Triple maceration process
In this maceration process, the
drug is macerated thrice by using the menstruum which is divided into three
parts in such a manner that the same volume for three parts in such a manner
that the same volume is used for each
maceratin.The quantity of menstruum required for three macerations is
calculateas follows:
Volume of menstruum required for
first maceration
Total vol. of menstruum - Vol. to be retained by the
drug Vol. to be
= + retained by the
3 drug
Volume of menstruum required for
2nd and 3rd maceration
Total vol. of menstruum
- Vol. of menstruum used in first maceration
=
2
·
The whole of the drug is macerated for one hour
with part of menstruum required for first maceration and strained.
·
The marc is macerated again for one hour with
the part of the menstruum required for 2nd maceration and strained.
·
The marc is macerated again for one hour with
the part of the menstruum required for 3rd maceration and strained.
·
The marc is pressed lightly.
·
The liquid obtained from 2nd and 3rd maceration
is pooled and evaporated to a specified concentration. This concentrated liquid
is mixed with the liquid obtained from the 1st maceration.
·
90 % alcohol equal to 1/4th of the volume of the
finished product is added.
·
Volume adjusted with water and allowed to stand
for 14 days and then filtered.
Examples
The following concentrated
infusions are prepared by triple maceration process:
1. Concentrated
Infusion of Quassia
2. Liquid
Extract of Senna
PERCOLATION PROCESS
1. Simple percolation process
2. Percolation process for
concentrated preparations
(a)
Reserved percolation
(b)
Modified percolation
3. Continuous hot percolation /
Soxhlet Extraction / Soxhlation
SIMPLE PERCOLATION
Apparatus:
Three types of apparatus are
generally used,
i)
Conical percolator
ii) Cylindrical
percolator
iii) Steam
jacketed percolator [for higher temperature extraction]
Stages:
1. Size reduction:
The drug to be extracted is
subjected to suitable degree of size reduction, usually from coarse powder to
fine powder, to
i)
increase the surface area of the drug exposed to the
menstruum,
ii) for
uniform packing of the percolator,
iii) to slow
down the movement of the menstruum and
iv) to
ensure complete exhaustion of the drug.
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2. Imbibition:
During imbibition the powdered
drug is moistened with a suitable amount of menstruum and allowed to stand for
four hours in a well closed container. During this period the drug swells up as
the menstruum penetrates the cell walls. The preliminary moistening of the drug
is necessary because:
i)
the dried tissue swells when it comes in contact with
the menstruum but if packed in the dry condition subsequent swelling will
reduce the porosity of the material and choke the percolator,
ii) the
air present in the interstices is removed by menstruum, which will otherwise
disturb the packing of the percolator due to which the menstruum will run
through the channels results in inefficient extraction,
iii) it
does not allow the fine particles to be washed out of the percolator during
percolation.
3. Packing:
After imbibition the moistened
drug is evenly packed into the percolator. Cotton wool or fibres of flax;
previously moistened with menstruum is placed on the perforated plate of the
percolator.
The packing should not be too
tight, it will lead to slow extraction rate. Similarly, loose packing will
allow the menstruum to pass through quickly resulting in incomplete contact
with the drug.
The drug should occupy 2/3rd
capacity of the percolator. After packing , a piece of filter paper is placed
over top of the bed, on which small quantity of washed sand is placed to
prevent disturbance of the packed material.
4. Maceration:
After packing sufficient menstruum
is added to saturate the material. When the liquid begins to drip from the
bottom of the percolator, the tap fitted at its bottom is closed. More
menstruum is added if required, so that a shallow layer of menstruum is
maintained over the drug bed.
The percolator is allowed to
stand for 24 hours to macerate the drug.
5. Percolation:
After 24 hours maceration, the
lower tap is opened and liquid collected therein is allowed to drip slowly at a
controlled rate until 3/4th volume of the finished product is obtained.
Sufficient amount of menstruum is
simultaneously added over the drug because at no time packed material should be
allowed to become dry. After collecting 3/4 th volume, the percolate is tested
for complete exhaustion of the drug by various tests.
Tests to check complete
exhaustion of the drug:
i)
Take a few ml of the last percolate and evaporate to
dryness, it no residue remains - it shows that the drug is completely
exhausted.
ii) The
specific gravity of last few ml of percolate is measured. If it is equal to the
specific gravity of the fresh menstruum the exhaustion is taken to be complete.
iii) Specific
chemical tests may be performed on the percolate for the drugs containing
alkaloids, glycosides, tannins, resins or bitter constituents.
·
The marc
is then pressed and the expressed liquid is added to the already
collected percolate.
·
More menstruum is added to produce the required
volume.
·
The liquid is then allowed to stand to settle
the suspended particles, decanted or clarified by filtration.
Examples:
i)
Tincture of belladonna
ii) Compound
tincture of cardamom
iii) Strong
tincture of ginger etc.
2.(a) RESERVE PERCOLATION
·
In this process, the first portion (about 3/4 th
of the final product) of the percolate which contains the maximum amount of
active constituents is reserved. Subsequently, percolation is completed as
usual until the drug is exhausted but the last part (about 1/4th of the final
product) is collected separately.
·
The second dilute part is then evaporated to get
a syrupy consistency which is then mixed with the reserved first portion of the
percolate.
·
Finally volume is adjusted by adding more
menstruum.
Example:
Liquid extract of liquorice
Advantages:
i)
The reserved part of the percolate which contains the
maximum amount of dissolved active principles is not subjected to heat, only
the dilute portion is evaporated. Hence, the major portion of the active
constituents of the drug are saved from deterioration.
ii) The
process is economical as the whole of the percolate is not evaporated.
2.(b) MODIFIED PERCOLATION
In percolation process for
preparation of tinctures the drug/percolate (d/p) ratio is about 1:4. The d/p
ratio is reduced to 1:3 by modifying the percolation process and hence, there
is a lot of saving in heat, time and menstruum.
Percolation is a displacement
process. The strong solution of active constituents of drug formed during
maceration is displaced by the fresh menstruum when percolation process is
started. It is proved that stationary menstruum (menstruum remaining in contact
with the drug) dissolves more menstruum is required to exhaust the drug when
simple percolation is used. But if continuous percolation stage has suitable
breaks by short maceration stages, the d/p ratio can be reduced to 1:3.
Example:
In simple percolation process:
Drug Imbibition Maceration Percolation and collect the
(1000 g) (for 4 hrs) (for
24 hrs) percolate, i.e.
3/4 the of the
volume
of finished preparation
Drug : Percolate = 1000
g :
4000 ml = 1 : 4
In modified percolation process:
Drug Imbibition Maceration Percolation and collect
(1000 g) (for 4 hrs) (for
24 hrs) 1000 ml of
percolate
Maceration Percolation & collect
(for
12 hrs) 1000 ml of
percolate
Maceration Percolation & collect
(for
12 hrs) 1000 ml of
percolate
Drug : Percolate = 1000
g :
3000 ml = 1 : 3
CONTINUOUS HOT PERCOLATION PROCESS / SOXHLET EXTRACTION / SOXHLATION
This process is used for those
drugs
·
where the penetration of the menstruum into the
cellular tissues is very slow and
·
the solute is not readily soluble into the
solvent and
·
the quantity of the menstruum is very less.
In such cases Soxhlet extractor
is used where small volume of hot menstruum is passed over the drug time and
again to dissolve out the active constituents until the drug is exhausted. The
process is known as Soxhlation.
Apparatus:
i)
A flask in which the menstruum is boiled,
ii) an
extraction chamber in which drug is filled, is fitted with side tube and a
siphon.
iii) a
condenser.
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The drug to be extracted , in
suitably comminuted form is usually packed in a ‘thimble’ made of filter paper which is then placed into the wider
part of the extractor.
N.B. thimble is used to prevent choking of the lower
part of the extractor.
Menstruum is placed in the flask
and boiled. The vapor rises through the side tube to the condenser, where the
vapor is condensed and fall on the packed drug, through which it percolates and
extract out the active constituents.
As the volume of menstruum in the
extractor increases, the level of liquid in the siphon also increases till it
reaches the maximum point from where it is siphoned out into the flask.
On further heating the menstruum
vaporizes while the dissolved active constituents remain behind in the flask.
The alternate filling and emptying of the body of the extractor goes on
continuously till the drug is exhausted. Thus the same quantity of menstruum is
made to percolate repeatedly, about 14 to 15 times through the drug and the
active constituents are collected in the flask.
Limitations of continuous hot percolation process:
1. Physical
character of the drug: If the physical character of the drug is such that
it would block the soxhlet apparatus then this method is not suitable. e.g
opium, gum, resin, orange peel etc.
2. Solvent:
Only pure solvents or constant boiling mixtures (like alcohol-water)can be used
for this purpose.
3. Chemical
constituents of the drug: The process is unsuitable for thermolabile active
constituents, e.g. enzymes, alkaloids, anthraquinone derivatives, esters etc.
Examples:
Soxhlation process of extraction is used to
i)
extract cantharidins from cantharides with benzene
ii) alkaloids
from the seeds.
INFUSION
This method is used for those
drugs
i)
which are soft in nature so that water may penetrate
easily to the tissues and
ii) the
active constituents are water soluble.
Apparatus:
Coffee-pot or tea-pot is the
simplest form of apparatus used for preparing infusion. Sometimes special pots
known as infusion pots are used for
the preparation of infusions. It consists of a loose perforated shelf resting
on a projection near the top of the pot.
Method:
In coffee-pot or tea-pot:
i)
The drug is placed at the bottom of the pot. Water is
added and it is well stirred three or four times during the period of infusion.
ii) Infusion
can also be prepared by enclosing the drug in a muslin bag and then suspending
it just below the level of water in a beaker. Stirring is not required in this
case because the water slowly circulates due to the increase in specific
gravity of water near the drug.
In infusion pot:
The drug is placed on the
perforated shelf. The pot is filled with water and the perforated shelf is
adjusted below the surface of water.
* Final volume is not
adjusted.
There are two types of infusions:
1. Fresh infusion, 2. Concentrated infusion
Fresh infusions:
A fresh infusion is an aqueous
solution of active constituents of a vegetable drug prepared by the process of
infusion e.g. Fresh infusion of Quassia.
Coarse powder of drug is used in
the preparation of infusion. Water is used as menstruum.
Pharmacopoeia states that fresh
infusion should be used within 12 hours after its preparation because it gets
spoiled due to fungal or bacterial growth.
Concentrated infusions
Concentrated infusions differ
from fresh infusions in that the concentrated infusions are prepared by maceration
or percolation process and alcohol is used either as a menstruum or as a
preservative.
An infusion containing 20 - 25 %
alcohol can be stored for sufficiently long time.
e.g. Concentrated compound
infusion of chirata and
Concentrated compound infusion of
gentian.
DECOCTION
Decoction is the process in which
the water soluble and heat stable constituents of hard and woody crude drugs
are extracted out.
Water is used as menstruum and
the drug, cut in small pieces, is boiled with the menstruum for 10 to 15
minutes.
After boiling, the liquid is
cooled and filtered, more water is passed through the marc to produce the
required volume.
Adjustment to final volume is
necessary to get a uniform product.
A freshly prepared decoction
should only be dispensed and the same must be consumed within 24 hours.
At present no decoction is
official in IP or BP.
DIGESTION
This process is a modified form
of maceration where the drug is extracted by heating at a particular pressure.
This will increase the penetration power of the menstruum, so that there is
complete extraction of the drug.
Apparatus:
The apparatus is known as
‘Digestor’ is a vessel made up of metal. The whole of the drug is placed in the
body of the digestor; placed the cover over it and bolted it with the help of
nuts.
The drug is treated with
menstruum for a definite period under specified condition of temperature and
pressure.
FACTORS
AFFECTING SELECTION OF AN EXTRACTION PROCESS
1.
Nature of the drug
The selection
of an extraction process mainly depends on the physical nature of the drug.
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Physical nature of the drug
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Extraction procedure
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·
Hard and woody
·
Soft drugs
·
Unorganised drug
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·
By percolation
·
By maceration
·
By maceration and not by percolation because
it may block the percolator.
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2. Cost of the drug
Costly drugs
are extracted by percolation whereas cheaper drugs may be extracted by
maceration. Cost involve in size reduction (i.e. comminuting) of the drug
should also be taken into consideration.
3.
Stability of drugs
Continuous hot
extraction process should not be used for those drugs containing thermolabile
active constituents.
4.
Therapeutic value of the drug
The drug
containing flavoring agents or bitters etc. which does not have much
therapeutic value may be extracted by maceration; but if the drug has
considerable therapeutic value then percolation process should be used.
5.
Nature of solvent
If the solvent
is water maceration is generally adopted but, if the solvent is volatile then
percolation process should be used.
6.
Concentration of the product
Dilute
preparations such as, tinctures may be prepared by maceration or by percolation
but, concentrated preparations such as, liquid extracts or dry extracts should
be prepared by percolation or reserved percolation process.
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EXTRACTION METHODS
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EXAMPLES
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A. MACERATION
i) Simple maceration
ii) Maceration
of unorganized drug / Maceration with adjustment
iii) Multiple Maceration
a)
Double maceration
b)
Triple maceration
B. PERCOLATION
i) Simple percolation
ii) Reserved percolation
iii) Continuous hot percolation / Soxhlation
C. INFUSION
i) Fresh infusion
ii) Concentrated infusion
D. DECOCTION
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i)
Tincture of Orange
ii) Tincture
of Lemon
iii) Tincture
of Squill.
i)
Tincture of Tolu Balsam
ii) Compound
Tincture of Benzoin
i)
Concentrated infusion of orange.
ii) Concentrated
infusion of chirata
iii) Concentrated
infusion of gentian
i)
Concentrated infusion of Quassia
ii) Concentrated
infusion of Senna
i)
Tincture of Belladonna
ii) Compound
tincture of cardamom
iii) Strong
tincture of ginger etc.
Liquid extract of Liquorice
i)
Cantharidin from cantharides
ii) Alkaloids
from seeds
Fresh infusion of Quassia
i)
Concentrated compound infusion of chirata
ii) Concentrated
compound infusion of gentian
No official preparations in IP or BP.
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DIFFERENCE BETWEEN MACERATION AND
DECOCTION
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Maceration
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Decoction
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1.
Menstruum may be water or hydroalcoholic solvents.
2.
The crude drug is macerated for 3-7 days.
3.
The drug is kept in contact with cold or warm
menstruum.
4.
After extraction the marc is expressed.
5.
Extra menstruum is not added to make up the required
volume.
6.
Alcohol acts as a preservative, hence it may be
dispensed after 24 hours also.
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1.
Menstruum is water.
2.
Just 10 to 15 minutes is required to complete the
process.
3.
Boiling water is passed through the crude drug.
4.
After extraction the marc is not expressed.
5.
Extra menstruum is passed through the extracted drug
to make up the volume.
6.
A freshly prepared decoction should be taken within
24 hours because microorganisms may grow in aqueous medium.
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Short note: EXTRACT
Extracts are concentrated preparations
containing the active principles of vegetable or animal drugs. The drugs are
extracted with suitable solvents and the product is concentrated to one of the
three types of extract -
Liquid extract - of which 1 ml usually contains the active
constituents from 1 g of the drug.
Dry extract - obtained by completely removing the solvent under
reduced pressure.
Soft extract _ obtained by evaporation to a plastic mass.
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Short note on EXPRESSION
The resudue of the drug after
extraction (often known as the marc) is saturated with solvent. To recover the
residual liquid pressure may be applied by a hydraulic press.
The marc is wrapped in cloth, is
placed in the perforated inner vessel, which is enclosed in another vessel
having an outlet for the expressed liquid. Application of hydraulic pressure to
the ram presses the marc against the fixed head, expelling residual liquid.
Comparison between extraction method:
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Extraction method
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Time for extraction
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Temperature
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Characteristics of the active constituents
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Maceration
Percolation
Digestion
Infusion
Decoction
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3-7 days
24 hours
Few days
Short period
15 mins
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Room temp
Room temp
Moderately high
Cold or boiling water
Boiling water
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·
Soluble in the menstruum
·
Heat stable / unstable
·
Soluble in the menstruum
·
Heat stable / unstable
·
Heat stable
·
Readily soluble
·
Water soluble
·
Heat stable
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THEORY OF EXTRACTION OF DRUGS
Mass transfer
Consider a crystal of soluble
material (e.g sugarcube) is immersedin asolvent in which it is dissolving. The
crystal will be surrounded by a stationary boundary layer of the solvent, with
the bulk of the fluid able to move.
The transport of molecules will
take place in two stages:
1.
The molecules will move through the boundary layer
by molecular diffusion, with no
mechanical mixing or movement.
2.
Once material has passed through the boundary
layer, mass transfer takes place by bulk movement of the solution, known as eddy diffusion.
Since there is no limit to the
vigor of the movement of the bulk of the fluid, so the rate controlling step is the molecular diffusion.
Mass transfer by molecular diffusion can be represented by
an equation, similar to conduction of heat transfer, in which
m DA(C1
-C2)
=
t h
where m = mass
transferred in time t
D =
diffusion coefficient of the solute
A = area of
the solute exposed to the solvent
C1 =
concentration of the solute at solid / liquid interface
C2 =
conentration of solute in the bulk phase
h =
thickness of the stagnant layer
Theory of extraction
of drugs
Examination of the extraction processes will show that all
have certain stages in common:
(i)
Suitable size reduction of the drug
(ii) Penetration
of the drug by the solvent
(iii)Solution of the soluble material
within the cells.
(iv)Escape of the soluble material
through the cell walls and through the solvent boundary layer surrounding the
particles of the drug.
(v) Separation
of the solution and the exhausted drug.
(I) Suitable size
reduction of the drug:
From the mass transfer equation
it is evident that m/t is proportional to A. If the area (A) is increased then
rate of dissolution also increases. So if the size of the drug (plant or animal
parts containing the active constituents) is reduced surface area will
increase, the consequence of which is the increase of the dissolution rate
(m/t) of the active constituent. The ideal
size reduction would be at
cellular level but it poses the following disadvantages:
(i) It
is difficult to reduce the size of a drug to its cellular dimension. It
requires costly instruments which may not be cost effective.
(ii) Obviously
it will take more time to reduce the size to such a level. Thus prolonged
comminution (size reduction) will produce heat that may damage the heat labile
constituents of the drug.
(iii)After extraction of such small particles they
will make a suspension which will be difficult to filter.
(iv)While reducing the size to cellular level it is
most probable that the cell walls will be broken and breakage of cell walls
will release unwanted cellular materials like gums, starch, proteins etc. which
may produce the filtrate cloudy by the release of colloidal material.
So the degree of size reduction
to be used will depend, therefore, on the botanical structure of the drug.
|
Name of the drug
|
Type of the drug
|
Degree of size reduction
|
|
Gentian
Cascara, Belladonna
Ipecacuanha
|
Soft
Moderately hard
Hard and woody
|
Sliced and bruised
Coarse and moderately coarse
powders
Moderately fine powder
|
(II) Penetration of the solvent into the drug:
Before drying the fresh drugs are
surrounde by a thin film of water. After drying that water film
evaporates and becomes porous due to shrinkage. The pores are
then occupied by air. To penetrate the cell wall the solvent must have
to displace the air first.
When the dry drug is moistened, the liquid film is again
renerated and then the cells imbibe the solvent and swell.
Sometimes to facilitate the
removal of air from the pores the solvent and the drug is first taken in a
vessel, vacuum is applied - thus air is removed from the pores. Then, when the
vacuum is released, pressure of the atmosphere forces the solvent into the drug
and penetration is facilated considerably.
(III) Solution of constituents:
Once the solvent has penetrated
into the cells solution of the constituents takes place and is governed by the solubility
of the constituents in the solvent and again solubility depends on the temperature.
So if the temperature is increased the solubility will also enhance.
(IV) Escape of the solution from the cells:
The solute molecules are
transferred through the boundary layer or stagnant layer. Factors controlling
mass transfer will show that the rate of extraction can be affected in the
following ways:
(i)
m / t ¥ 1 / h i.e.
if the thickness of the boundary layer can be reduced rate will ne increased. h
can be reduced by agitating the mixture occassionally which disperses local
concentrations of the solution, thereby, increasing the concentration gradient.
(ii)
By suspending the drug in a cloth bag or placing it
on a perforated plate near to the surface of the liquid the escape of the
solution can be hastened. As the constituents dissolve, the density of the
solution increases, so that convection currents are established, leading to
circulation of the solution followed by the reduction of local concentration
surrounding the cloth.
(V) Separation of solution and exhausted drug:
After dissolution the solid
materails has to be strained off. Since, the drug absorbs solvent and there is
a residue of soluble constituents in that solvent, so the drug is subjected to
pressure and sometimes under hydraulic pressure.
PROPERTIES OF SOLVENTS USED FOR
EXTRACTING DRUGS
The ideal solvent would be:
1.
It must be cheap.
2.
Non-toxic
3.
It should be
stable chemically and physically.
a)
neutral to reaction
b)
not too volatile
c)
non-inflammable
4.
Selective, i.e. it should remove the desired
constituents with minimum amount of the inert materials.
N.B.
·
Many extracts are intended for internal use. So
the solvents should be selected cautiously.
·
All the above properties of an ideal solvent
render the majority of the organic solvents unsuitable.
·
In special cases petroleum ether is required to
remove the fat from a drug before extracting
(e.g. some seeds containing fatty coating) the desired active
constituents.
Water as a solvent for extraction:
Advantages:
(i) It
is cheap.
(ii) It has a
wide solvent action (e.g. protein, coloring maters, gums, antharaquinone
derivatives, most alkaloidal salts, glycosides, sugars and tanins).
(iii)It
is non-toxic and can be taken internally.
It is non-inflammable. In
industry handling of large volume of volatile solvents may cause accident.
Hence the inflammability of a solvent is very important from the point of view
of industry.
Disadvantages:
(i) It
is not selective. It dissolves a wide range of substances that may interfere with the extract’s clarity e.g.
gum, protein (coagulated).
(ii) Water
is good medium for mold and bacterial growth. Generally most preparations are
preserved with a small amount of glycerine, chloroform or by sterilization.
(iii)Water promotes hydrolysis of many substances and
allows enzymatic actions to take place [e.g glycosides such as digitalis].
(iv)Concentration of aqueous solution requires more
heat than for most other solvents due to its higher latent heat of evaporation
(537 cal / gm).
Ethanol as solvent:
Advantages:
(i) Reasonably
selective, e.g. in a drug containing gum, albuminous matter and a glycoside or
an alkaloidal salt, ethanol in a suitable dilution with water would dissolve
only the glycoside or the alkaloidal salt, whereas water would usually dissolve
all of the constituents.
(ii) Molds
cannot grow in solvent mixture containing more than 20 % ethanol.
(iii)Non-toxic in the quantities prescribed in the
medicinal preparations.
(iv)It is neutral, hence compatible with other
products .
(v) Latent
heat of vaporization is less than water , so less heat will be consumed to make
an extract concentrated.
(vi)Can
be mixed in any combination with water.
Disadvantage:
Cost due increases due to the
duty imposed by the Government on it
Questions
Ques. 1 How will you make an infusion of Gentian? (1991) 8
Ans:- See the method for Fresh infusion.
Ques. 2. Write the principle, method and equipment used in the
following preparations:-(i) Tincture Belladonna (1992) 4
(ii)Tolu
Balsam syrup. (1992) 4
Ans:- Tolu balsam is an
unorganized drug. Tolu balsam is taken on a tared vessel and boiling purified
water is added to it. The vessel is tightly closed and boiled gently for 30
minutes, stirring frequently. Purified water is added to adjust the specified
weight. The preparation is cooled and filtered and then sucrose is added to it.
It is heated again in water bath to dissolve the sucrose. Finally sufficient
purified water is added to produce the required volume.
Tolu syrup has some aromatic
odour and flavour and it is believed to have a mild expectorant action.
Ques. 3. Discuss what do you mean by extraction. How triple percolation
is conducted? (1993) 4+12
Extraction may be defined as the
process in which the animal or plant tissue are treated with specific solvents
whereby the medicinally active constituents are dissolved out, cell tissues and
most of inactive or inert components remain undissolved. The solvent used for
extraction purpose is known as menstruum and residue left after extraction the
desired constituents is known as marc.
The various processes used for
extraction are: 1. Infusion, 2. Decoction, 3. Maceration, 4. Percolation, 5.
Digestion.
The various preparations prepared
by using one of the above methods are Infusions, Decoctions, Spirits, Elixirs,
Extracts etc. All these preparations are commonly known as ‘Galenicals’.
Triple percolation:- Write
Modified Percolation Process.
Ques.4. Describe the percolation process in details with a schematic
diagram of a typical percolator. (1994,
1996) 12
Ans:- Simple percolation process.
Ques 5 What is reserved percolation? (1994) 4
Ans:- Reserved percolation
process.
Ques.6. Short notes on Maceration and Decoction. (1994) 8
Ans:- Write the difference
between Maceration and Decoction.
Ques. 7. Short note on Soxhlet extractor with diagram. (1994) 8
Ans:- Soxhlet apparatus with diagram.
Ques. 8. Factors affecting the choice of extraction process. (1994) 8
Ans:- Factors affecting the
choice of extraction process.
Ques.9. How does the method of preparation vary for concentrated
infusion and infusion. (1995)
Ans:- See ‘Infusion’.
Ques. 10. Difference between infusion and decoction? (1995) 2
Ans:- Write yourself.
Ques. 11. What do you by leaching? Name the methods used for the same
mentioning their procedure. (1995) 4+12
Ans:- “Leaching” is same as
“Extraction”.
Two main methods of leaching are
maceration and percolation. Give the description briefly with diagram.
REFERENCE
1. Introduction
to Pharmaceutics - A.K.Gupta [Diploma - 1st year]
2. Pharmaceutics
- R. M. Mehta [Diploma - Ist year]
3. Remington’s
Pharmaceutical Sciences.
4. Cooper
& Guns Dispensing
5. Cooper
& Gun’s Tutorial.
6. Bentley’s
Text Book of Pharmaceutics.