Pharmaceutics-I (Physical Pharmacy)

by
AMK
Contents
• Introduction
• Types of extraction
 Solid- Liquid extraction (Leaching)
 Maceration (purpose & process)
 Percolation
 Industrial / Large Scale
 Liquid-liquid extraction (Partitioning)

• Factors affecting choice of extraction process

• Summary
 Introduction
• Extraction may be defined as:
“Removal of soluble materials from an insoluble residue, either liquid or solid, by
treatment with a liquid solvent”
“Process in which the animal or plant tissues are treated with specific solvents
whereby the medicinally active constituents are dissolved out, cell tissues and most
of inactive or inert components remain undissolved.”
“Withdrawal of dissolved constituents from crude drugs through the use of
selective solvent in which the desired constituents are soluble.”
• Solvent used for extraction  Menstruum
• Residue left after extraction  Marc
• The extraction of a soluble constituent from a solid by means of a solvent is
commonly referred as leaching, but the general term EXTRACTION is
most frequently used in pharmaceutical practice.
 Solvents for Extraction
• Most commonly used solvents for extraction: Water, Alcohol and their dilutions
• Characteristics of ideal solvent:
1. Cheap
2. Physically and chemically inert
3. Selective i.e. should dissolve the desired constituent only with minimum
amounts of the inert substances
4. Non-toxic
• Water is non-selective, good media for growth of bacteria and molds,
require more heat to concentrate the liquid extracts and can lead to
hydrolysis
• Alcohol (Ethanol) is reasonably selective, bacteria and molds cannot grow
in solutions containing 20% or more of alcohol, non-toxic in the quantities
present, BUT costly as compared to water
 i. For organized drugs (Simple
Maceration)
a. Simple extraction
ii. For unorganized drugs (Maceration With
Adjustments)
1. Maceration
a. Double Maceration
b. Multiple extraction
b. Triple Maceration
Solid-Liquid

i. Simple percolation
Extraction

2. Percolation ii. Reserved percolation

iii. Continuous hot percolation process or soxhelt extraction

i. Multiple stage extraction

3. Industrial
ii. Circulatory extraction
Scale/Large Scale

iii. Extraction battery

Crude Drug

i. Organized
Crude drugs with specific cell structures, like
roots, stems, leaves, flowers etc.

ii. Unorganized
Drugs having no cellular or tissue structure
and are obtained from plants as their
exudates like gums, mucilage, resins etc.
Extraction processes
• It is a prolonged infusion in which drug is soaked in the
Maceration menstruum for 2-14 days

• Crude drug is placed in container (percolator) and menstruum

Percolation is added from top, which gets the active ingredients along
with it

• It is a form of maceration, which consists of application

Digestion of gentle heat

• It involves boiling of drug with water for a given time

Decoction period

• It involves pouring of hot water over drug, allowing it to

Infusion stand for sufficient time and temperature
Maceration
• The word maceration comes from a Latin word “macerare” meaning “to
soak”.
Basic Principle:
• It is a process in which the properly comminuted drug is permitted to soak
in menstruum until the cellular structure is softened and penetrated by the
menstruum and the soluble constituents are dissolved.
• Menstruum refers to the solvent, which is used to extract ingredients from
plant or animal origin.
• Generally, this method involved:
Introduce drug with solvent in bottle 
Stopper tightly and agitated occasionally for 2-14 days 
Pour off the liquid and express the residue 
Filter the mixed liquid
Simple Extraction
i. For organized drugs (Simple Maceration)

Take solid crude drug (coarse powder)

Take menstruum and add crude drug into it

Macerate for 7 days with occasional shaking

Obtain the extract, press the marc and combine the filtrate and expressed liquid

Stand the combined liquid for some time, followed by filtration or decantation
• Examples:
Tincture of squill
Tincture of lemon Squill
 Tincture of orange
 Tincture of gentian (root)

Gentian
• ii. For unorganized drugs (Maceration With Adjustments)

Take powdered drug

Add menstruum (3/4 parts)

Macerate the drug for 2-7 days with occasional agitation

Filter the menstruum

Add remaining menstruum through filter paper (having unpressed marc)

Adjust the final volume

• Examples:
Tincture of benzoin
Tincture of tolu
Tolu
 Tincture of myrrh

Benzoin
• IMPORTANT
Marc is NOT pressed
Multiple Extraction
• Multiple maceration OR Repeated maceration OR maceration process for
concentrated preparations
• More effective than simple maceration ( as left amount of drug in marc
during 1st cycle of maceration can be extracted out during the next
maceration)
• Solvent  Alcohol
• Repeated maceration is done by:
a. Double Maceration (E.g. Conc. Infusion of Gentian)
b. Triple Maceration (E.g. Liq. Extract of Senna)
Double Maceration
• The maceration of drug is carried out twice
• The total volume of menstruum is subdivided in 2 parts in such a way that
same quantity of menstruum is used for each maceration.
• The marc press and the liquid obtained after 1st and 2nd macerations are
combined together, filtered and evaporated to get the product of required
concentration.

EXAMPLE:
• Concentrated compound infusion of gentian
 Triple Maceration
• The maceration of drug is carried out thrice
• The total volume of menstruum is subdivided in 3 parts in such a way that same
quantity of menstruum is used for each maceration.
IMPORTANT:
• The marc is pressed after 3rd maceration
• Liquid (macerate) obtained after 2nd and 3rd macerations are combined together
and evaporated before adding in the 1st macerate

EXAMPLE:
• Concentrated infusion of Quassia (bark)
• Liq. Extract of Senna leaves
 Percolation
• Percolation comes from the Latin word percolare, which means "to strain
(filter) through."
• Percolation happens when liquid is strained through a filter, like when someone
makes coffee, in which:
• Soluble compounds leave the coffee grounds and join the
water to form coffee.
• Insoluble compounds (and granulates) remain within
coffee filter.
 Percolation
• In this process, the raw material is packed into column and solvent is allowed to
percolate through it
Basic Principle:
• In percolation, suitably comminuted drug is moistened with sufficient quantity
of menstruum, which is then packed in a percolator. The drug is allowed to
remain in contact with menstruum for 24 hours, more menstruum is added
from the top and percolation is started. The required volume is collected, marc
is pressed and expressed liquid is added to the percolate. The required volume
is produced by adding more of menstruum and the mixed liquid is clarified by
decantation or filtration.
Example: tincture of belladonna, cardamom, ginger
PERCOLATION
Stages of Simple percolation:
Size reduction or comminution of drug

Imbibition or moistening of drug

Packing

Maceration

Percolation
 Size reduction or comminution of drug
• Drug to be extracted is subjected to size reduction, from:
coarse powder  fine powder

• Reasons:
 to increase surface area
For uniform packing of percolator
To slow the movement of menstruum
To ensure complete exhaustion of drug
 Imbibition or moistening of drug
• The drug is moistened in suitable amount of menstruum and allowed to
stand for approx. 4 hours in a well closed container
• During this period the drug swells up and menstruum penetrates the cell
walls.
• After the lapse of time, the moistened drug is passed through a coarse
sieve to remove the lumps and to mix the dry powder
• Reasons:
 Choking of percolator, if dried drug is placed in the percolator as such
- The dried tissue swells when it come in contact with menstruum but if packed
in the dry condition, subsequent swelling will reduce the porosity of the
material and choke the percolator.
 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 mainly through the channels resulting in inefficient
extraction.
 It prevents the fine particles to be washed out of the percolator during
percolation.
 Packing

• After imbibition, the moistened drug is evenly packed in the percolator

• Percolator:
A percolator is a conical vessel
having a lid at the top
 is provided with a false bottom on which filter paper or cotton wool is
placed to support the column of the drug.
The base of the percolator is fitted with a tap from which the percolate is
collected.

• Two types of percolators are available:

PERCOLATION
 Packing
OPEN PERCOLATOR CLOSED PERCOLATOR

• used when the menstruum is • used when the menstruum is

water or dilute alcohol. volatile e.g. alcohol, ether etc.
• cheap and easy to handle.
 Packing
• A piece of cotton wool etc. (previously moistened with menstruum) is placed on
the false bottom of the percolator.
• A small amount (about 10%) of the moistened drug is introduced into the
percolator
• It is pressed lightly with rod or any other suitable device, to give even
compression.
• More moistened drug is introduced and pressed till whole of the drug is packed
in the percolator.
• After suitable packing of the drug into the percolator a piece of filter paper is
placed over top of it
• small quantity of washed sand is placed over filter paper to prevent disturbance
of the packed material
 Packing
Important Precautions….
• The packing should NOT be:
 Too tight
 It will not allow the menstruum to pass freely which will lead to slow extraction
rate.
 Too loose
 Loose packing will allow the menstruum to pass through quickly resulting in
incomplete contact with the drug leading to less dissolution of active
constituents (inefficient extraction).
• It should be ensured that the drug should occupy about 2/3rd capacity of the percolator.
 Maceration
After packing, sufficient menstruum is added to saturate
the material

Top of the percolator is covered with a lid.

When the liquid begins to drip from the bottom of

percolator, the tap (fitted at its bottom) is closed.

More of menstruum can be added at the top to maintain

a layer of menstruum over the drug.

The percolator is then set aside for 24 hours to macerate

the drug.
 Maceration
 Precaution:
- Column should NOT be allowed to dry otherwise cracks will appear
in the packed column, resulting in inefficient percolation.

The 24hrs maceration period helps the menstruum to penetrate deep into
the tissues and dissolve the maximum amount of active constituents and
Drug will be extracted with comparatively small volume of menstruum.
 Percolation
After 24 hours maceration of the drug, the lower tap is opened

3/4th volume of the menstruum is obtained

At the same time more menstruum is added over the drug and Menstruum is collected again

The marc is then pressed and expressed liquid is added to the already collected liquid

The liquid is then allowed to stand to settle the suspended particles

Finally, the liquid is decanted or clarified by filtration

 Percolation
 Following tests can be applied to check for complete exhaustion of the drug :

Take a few ml of the last percolate and evaporate to dryness, if no

residue remains this shows that the drug is completely exhausted.

Measure the specific gravity of last few ml of percolate, if it is equal to

the specific gravity of the menstruum, it shows exhaustion of the drug.

Specific tests may be performed on the percolate for the drugs

containing alkaloids, glycosides, tannins, resins or bitter constituents.
 Percolations for concentrated preparations
1. Reserved Percolation
• 1st portion (about 3/4th of the final product) of the percolate which contains
the maximum amount of active constituents is reserved as such
• Last 1/4th of final volume is collected separately, evaporated to get syrupy
consistency.
• The above part is then mixed with the reserved percolate and the final
volume/ required concentration is then adjusted.
• Menstruum: Alcohol
Uses:
• For the preparation of liquid extracts (e.g. Liquorice Liquid Extract)

Advantages:
• Economical process (as whole of the percolate is not evaporated)
• Reserved percolate is not subjected to heat for evaporation
 Percolations for concentrated preparations
2. Continuous hot Percolation or Soxhlet Extraction
• This continuous extraction process combines the two normal operations of
simple extraction i.e. extraction and evaporation
• That is, immediately after contact with drug, the solution is evaporated and
vapors taken to a condenser, where the condensed liquid is returned to drug to
continue extraction
• Thus, with the help of temperature, smaller volume of solvent may be used
and the process of extraction may be called continuous extraction.
• Used in cases where:
 The penetration of the menstruum into the cellular tissues is very slow
 The quantity of menstruum is very less.
 The solute is NOT readily soluble into the solvent

• Apparatus used: Soxhlet extractor

• In this case, small volume of hot menstruum is passed over the drug time
and again to dissolve out the active constituents until the drug is
exhausted. This process is known as Soxhlation.
• IMPORTANT  the volume of solvent is used again and again with the
help of special apparatus OR solvent recycling
• Soxhlet apparatus, consists of three parts :
 a flask in which the menstruum is boiled
 an extraction chamber in which drug is filled, is fitted with a
side tube and a siphon
 a condenser
• Vapors pass through side tube, enters condenser where they are
condensed, fall back on the packed drug in the extraction
chamber, percolates and extracts out the active constituents
• As the volume of menstruum in the extractor increases, volume in
siphon also increases, till it falls back into the flask
• Further heating vaporizes the Menstruum & Active ingredient remain
behind in the flask.
• Filling and emptying of extractor goes on continuously and the process is
repeated for 14-15 times through the drug and active constituents are
collected in the flask.
Disadvantage: NOT suitable for thermolabile constituents
 SOXHLET APPARATUS

Condenser

Extraction
Siphon Chamber

Flask

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 Industrial scale (Large scale) extraction
procedures
i. Circulatory extraction
ii. Multiple stage extraction
iii. Extraction battery
 i. Circulatory extraction
• Process is so called because the Solvent is continuously
circulated through the drug.
• Solvent is pumped from the bottom of the vessel to the inlet
where it is distributed through spray nozzles over the surface
of the drug.
• The movement of the solvent reduces boundary layers and the
uniform distribution minimizes local concentrations leading to
more efficient extraction in a shorter time.
• Like the normal maceration process however, the extraction is
incomplete, since mass transfer will cease when an equilibrium
is set up.
• This problem can be overcome by using a multi-stage process
45
 ii. Multiple stage extraction
The equipment includes:
• vessel for the drug
• circulating pump
• spray distributors
• a number of tanks to
receive the extracted
solution

46
• The extractor and tanks are connected
with piping and valves as shown in Fig
• Such that any one of the tanks may be
connected to the extractor for the
transfer of solution.
Procedure:
1. Fill extractor with drug, add solvent
and circulate. Run off to receiver 1.
2. Refill extractor with solvent and
circulate. Run off to receiver 2.
3. Refill extractor with solvent and
circulate. Run off to receiver 3.
4. Remove drug from extractor and
recharge. Return solution from 1 to
extractor. Remove for evaporation.
5. Return solution from 2 to
extractor and circulate. Run off to
receiver 1.
6. Return solution from 3 to
extractor and circulate. Run off to
receiver 2.
7. Add fresh solvent to extractor
and circulate. Run off to receiver 3.
8. Remove drug from extractor and
recharge.
9. Repeat cycle.
• Each batch of drug is treated several times with solvent
• The receivers contain solution with the strongest in receiver 1 and the
weakest in receiver 3
Advantages
• The drug is extracted as many times as there are receivers
• If more extraction stages are required, it is only necessary to have more
receivers
• The last treatment of the drug before it is discharged is with fresh solvent,
giving maximum extraction
• The solution is in contact with fresh drug before removal for evaporation,
giving the highest possible concentration

49
iii. Extraction battery
• In the normal percolation process, the percolate is not of the maximum
concentration.
• Solvent percolates through the whole of the bed, Flow will occur through the
upper layers and will continue until the lowest layer is also exhausted
• As a result, the final runnings of the percolate are dilute (though max
exhaustion took place)
• The ideal situation would be to have countercurrent movement of the
solvent and the drug whereby:
• the drug is removed immediately after it has been treated with fresh solvent,
• While fresh drug is added, contacting the outgoing solution to give maximum
concentration.

50
• Continuous extraction devices are used in some industries where large
amounts of a single material are handled
• For example, the extraction of sugar from sugar beet.

• Pharmaceutical practice demands flexibility. Batches of different size

and materials can be treated as a stage-wise process, so that a series of
vessels is used but the extraction is semi-continuous.
• The equipment is described as an extraction battery
• Consists of a number of vessels with interconnecting pipework
arranged in such a way that solvent can be added to, and the product
taken from any vessel.
• These vessels can, therefore, be made into a series with any one of
the vessels as the first of the series.

51
• Arrows indicate transfer of material
to or from the vessels.

• Key:
• F - fresh drug.
• S -solvent.
• P- product.
• E- exhausted drug.

• A, B, C extraction vessels. Start

with C empty and units A and B
containing drug, with A more nearly
exhausted.
 I IV
1. Charge fresh drug to C. 1. Remove product solution from A.
2. Transfer solution from B to C. 2. Transfer solution from C to A.
3. Transfer solution from A to B. 3. Transfer solution from B to C.
4. Add fresh solvent to A. 4. Dump exhausted drug from B.
II V
1. Remove product solution from C . 1. Charge fresh drug to B.
2. Transfer solution from B to C. 2. Transfer solution from A to B.
3. Transfer solution from A to B. 3. Transfer solution from C to A.
4. Dump exhausted drug from A. 4. Add fresh solvent to C.
III VI
1. Charge fresh drug to A. 1. Remove product solution from B.
2. Transfer solution from C to A. 2. Transfer solution from A to B.
3. Transfer solution from B to C. 3. Transfer solution from C to A.
4. Add fresh solvent to B. 4. Dump exhausted drug from C
53
Most important points….
• The last treatment of the drug before it is discharged is with fresh solvent, giving
maximum extraction
• The solution is in contact with fresh drug before removal for evaporation, giving
the highest possible concentration
Liquid- Liquid Extraction
• It is also referred to as Solvent extraction or Partitioning.
• In solvent extraction, two immiscible liquids are shaken together.
• Often the solute is miscible in one solvent and immiscible in the other
solvent.
• Based on the statement "like dissolves like“:
More polar solutes dissolve in  more polar solvent OR Aqueous phase
Less polar solutes in  less polar solvent OR Organic phase
• All of these solvents form a clear delineation between the two liquids. ( in
separating funnel)
Applications:
Separation of organic substances from aqueous solution
e.g. Extraction of alkaloids
Purification of antibiotics
Production of bacitracin

• Large scale  Stirred tanks, Podbielniak extractor ( aka ‘‘pod’’

centrifugal extractor, provides differential countercurrent
extraction)
• Lab scale  Separating funnel
Separating funnel: Cone shaped apparatus with a hemispherical
end, with stopper at the top and stopcock (tap), at the bottom.
• the two phases (and the mixture to be separated
in solution) are added through the top with the tap
at the bottom closed.
• The funnel is then closed and shaken gently by
inverting the funnel multiple times. The funnel is
then inverted and the tap carefully opened to
release excess pressure.
• The separating funnel is set aside to allow for the
complete separation of the phases.
• The stopper and the bottom tap are then opened
and the lower phase is released by gravitation.
• When the bottom layer has been removed, the tap
is closed and the upper layer is poured out through
the top into another container.
Recovery of solvent from marc
• If it is not a part of extraction process, then the
basic procedure for the recovery of solvent from
marc is the application of Pressure.
• Preliminary equipment used Hydraulic press
• Procedure: Marc wrapped in cloth is placed in
perforated inner vessel having an outlet for
expressed liquid. Application of hydraulic pressure
presses the marc against fixed head, expelling the
residual liquid.
• Further recovery:
special forms of distillation equipment
vacuum oven

• Most preferable Option is the recover the

solvent directly from drug while still in
extraction vessel
using steam jacket
Allow steam entry in the extraction
vessel from base (better method)
Factors effecting selection of an Extraction process
• Percolation for hard and woody drugs (Nux vomica)
1. Nature of drug • Maceration for soft drugs & unorganized drugs (Gentain & Benzoin)

• Percolation for costly drugs (Ginger)

2. Cost of drug • Maceration for cheaper drugs

• Continuous hot extraction procedures should not be used if the active

3. Stability of drug constituent is thermolabile

• Percolation for drugs with considerable therapeutic value (Belladona)

4. Therapeutic value of drug • Maceration for drugs containing flavoring agents etc. (lemon)

• Percolation in case of volatile solvents

5. Nature of solvent • Maceration (generally) if water is used as solvent

• Percolation for concentrated preparations e.g. liquid extracts, conc.infusions

6. Concentration of the product • Both Maceration and Percolation for dilute preparation e.g. tinctures
References
 Introduction to pharmaceutics-I, by Gupta
 Tutorial Pharmacy, by Cooper & Gunns