CHAPTER
3
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
 |
 |
 |
|||
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.
 |
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.
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.
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.
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.
Physical nature of the
drug
|
Extraction procedure
|
· Hard and woody
· Soft drugs
· Unorganised drug
|
· By percolation
· By maceration
· By maceration and not by percolation because it may block the
percolator.
|
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.
EXTRACTION
METHODS
|
EXAMPLES
|
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
|
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.
|
DIFFERENCE
BETWEEN MACERATION AND DECOCTION
Maceration
|
Decoction
|
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.
|
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.
|
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.
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:
Extraction method
|
Time
for extraction
|
Temperature
|
Characteristics of the active constituents
|
Maceration
Percolation
Digestion
Infusion
Decoction
|
3-7 days
24 hours
Few days
Short period
15 mins
|
Room temp
Room temp
Moderately
high
Cold or
boiling water
Boiling water
|
·
Soluble in the menstruum
·
Heat stable / unstable
·
Soluble in the menstruum
·
Heat stable / unstable
·
Heat stable
·
Readily soluble
·
Water soluble
·
Heat stable
|
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.
