Extraction_Physical Pharmacy_2nd sem_HAN.pdf

EXTRACTION
a. Maceration: Purpose & process.
b. Percolation: Purpose and Process.
c. Liquid-Liquid extraction: Purpose and Process.
d. Large scale extraction: Purpose and Process

Extraction
• “The removal of soluble substances from non-
soluble residues, either liquid or solid, by
treatment with a liquid solvent.”
• Liquid/Liquid extraction
• Solid/Liquid extraction
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Dr. Hafiz Awais Nawaz (Physical Pharmacy-II
Extraction)
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Extraction
• The separation of medicinally active portions of
plant or animal tissues from the inactive or inert
components by using selective solvents.
• In this method the wanted components are
dissolved by the use of selective solvents known
as menstrum & undissolved part is a marc.
• After the extraction unwanted matter is removed.
Marc: Solid residue obtain after extraction
Menstruum: Solvent used for extraction
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Liquid/Liquid Extraction
• Refer to partition co-efficient (1st semester)
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Theory of Drug Extraction
• Common stages are
Suitable size reduction of the drug.
Penetration of the drug by the solvent.
Solution of the soluble matter within the cells.
Escape of the dissolved material through the
cell walls and through the solvent boundary
layer surrounding the particles of the drug.
Separation of solvent and exhausted drug.
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1. Suitable size reduction of the drug
Generally, large surface area is desired, but not possible for many
reasons:
• Size reduction to much extent is difficult.
• Prolonged size reduction leads to drug deterioration or loss of
volatile constituents.
• Cell breakage would lead to ‘leakage’ of undesired constituents that
may otherwise would have ‘filtered’ by intact cell walls.
• Degree of size reduction depends on botanical structure.
o Sliced and bruised condition (Soft drugs like Gentian)
o Coarse or moderately coarse powders (Cascara or Belladonna)
o Moderately fine powder (Hard and woody drug like Ipecacuanha)
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1. Suitable size reduction of the drug
• Greatest degree of size reduction is not preferred. Extracts
from Belladonna moderately coarse powder gives better
alkaloidal content as compared to fine powder.
• An appropriate size reduction will comply the following
requirements:
 Cause some cells of the drug to be broken to assist
penetration of the solvent and escape of soluble matter.
 For similar reasons, cause some cells to be cracked or
distorted.
 Results in particles having a large enough surface area for
adequate mass transfer.
 Provide a particle size that will not result in a very long path
for the solvent and the soluble matter.
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2. Penetration of the drug by the solvent
• Drug in dry state is porous due to shrinkage, and must be
displaced with solvent. It can be facilitated by removing the
air through vacuum.
• Spiral shaped fibrils of cellulose cell wall are surrounded by
thin water layer. On drying the film is lost and fibers move
together. By adding solvent reverse happens.
• Swelling occurs by distension of cells. More swelling for
thin-walled cells as compared to thick-walled cells.
• Plant tissue swells by the addition of solvent. Higher
swelling is observed with drugs having higher number of
hydroxyl groups.
• Glycerol shows comparable swelling with water but due to
high viscosity it takes longer time.
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3. Solution of the soluble matter
within the cells
• Once solvent has penetrated into the cells,
solution forms.
• It depends on
Solubility profile
Rate of solution formation
Temperature action
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4. Escape of the solution from the
cells
• During size reduction process many cells are broken and do not
impede the process.
• In the intact cells, osmosis and diffusion are the most likely
processes.
• The dissolved substances must pass through boundary layer of
solid/liquid interface.
• Rate of diffusion will depend on concentration gradient, thickness
of boundary layer and diffusion co-efficient.
1. Rate of diffusion can be enhanced by (Drug is immersed in solvent)
i. Agitating the mixture occasionally.
ii. Agitating the mixture continuously, may be with a pump.
iii. By suspending the drug in a cloth bag near the liquid surface.
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4. Escape of the solution from the
cells
2. Solvent flows past the drug particles:
• The flow replaces the solution by pure solvent causing
an increase in concentration gradient.
• Solvent flows through passages and reduced the
boundary layers.
3. Increased temperature will have following advantages:
 Solvent viscosity will decrease and will decrease the
boundary layer.
 Convection currents will generate and enhances
extraction process.
 Diffusion co-efficient is directly proportional to
temperature and inversely proportional to viscosity.
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5. Separation of solution and
exhausted drug
• The solid material has to be strained off.
• Solid residue (Marc) is subjected to pressure
to expel as much of extracted drug as
possible.
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Menstruum (Solvent for Extraction)
Ideal solvent for extraction would be
• Cheap
• Non-toxic
• Stable, chemically and physically inert, not too volatile
and non-inflammable.
• Selective, that is, to remove the desired active
constituents, with the minimum amount of the inert
materials.
 Most of organic solvents cannot be used for oral use, but
can be used if not remain within product e.g. removal of
fat from drug.
 Water and ethanol are most commonly employed.
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Water as solvent
• Water is a solvent for proteins, coloring
matters, gums, anthraquinone derivatives,
most alkaloidal salts, glycosides, sugars and
tannins.
• In addition, water will dissolve enzymes, many
organic acids, most organic salts and small
proportions of volatile oils.
• Waxes, fats, fixed oils and most alkaloids (free
bases) are insoluble.
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Water as solvent
Advantages:
• Cheap
• Wide solvent action
• Non-toxic
• Non-inflammable
Disadvantages:
Not-selective.
Good medium for bacterial and fungal growth.
Promotes hydrolysis of many substances, allow enzyme
actions.
Concentration of water based extract require more heat.
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Ethanol as solvent
• Alcohol is a solvent for alkaloids, alkaloidal
salts, volatile oils and resins, coloring matters,
tannins, anthraquinone derivatives, many
organic acids and salts.
• Ethanol does not dissolve albuminous matter,
gums, waxes, fats, and most fixed oils, sucrose
in insoluble, but certain other sugars (e.g.
dextrose) are soluble.
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Ethanol as solvent
Advantages:
• Reasonably selective
• Molds and bacteria cannot grow (20% or more)
• Non-toxic in the quantities present in medicinal doses of
preparations.
• Neutral, compatible with most of other solvents and
preparations.
• Ethanol promotes rapid absorption of the constituents.
• Latent heat of vaporization is lesser than water.
• Miscible with water in all proportions.
Disadvantages:
Principal disadvantage is cost, as compared to water.
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Methods of extraction
1. Infusion
2. Decoction
3. Digestion
4. Maceration
5. Percolation
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1. Infusion
• Fresh infusions are prepared by macerating
the crude drug for a short period of time with
cold or boiling water. These are dilute
solutions of the readily soluble constituents of
crude drugs.
Types of Infusion :
• Fresh Infusion : e.g. Infusion of orange
• Concentrated Infusion : e.g. Concentrated
infusion of Quassia.
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2. Decoction
• In this process, the crude drug is boiled in a
specified volume of water for a defined time;
it is then cooled and strained or filtered.
• This procedure is suitable for extracting water-
soluble, heat stable constituents.
• e.g. Tea , Coffee
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3. Digestion
• This is a form of maceration in which gentle
heat is used during the process of extraction.
• It is used when moderately elevated
temperature is not objectionable.
• The solvent efficiency of the menstruum is
thereby increased.
• e.g. Extraction of Morphine
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4. Maceration
• 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
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Maceration: Process steps
Plant
material
Closed
vessels
Stand for 3-7
days
Solid residue
pressed
Clarified
Crushed,
small pieces,
moderate or
coarse powder
Menstruum
Liquid strained
off
Strained liquid mixed
with expressed liquid
Evaporation and
concentration
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Maceration
Merits
Small sample size.
Strong swelling properties or high mucilage.
Energy saving process.
Demerits
Not exhaustively extract the drug.
It is very slow process.
Solvent required is more.
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Factors affecting choice of extraction
process
• Character of the drug:
Drug character Extraction process
Hard and tough (e.g. Nux vomica) Percolation
Soft and Parenchymatous (Gentian) Maceration
If un-powderable (Squill) Maceration
If unorganized (Benzoin) Maceration
If preferable to avoid powdering (Senna Maceration
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process
Therapeutic value of the drug:
• High therapeutic value (Belladona), percolation is preferred,
multiple extractions are employed.
• Otherwise, maceration is adequate and multiple extractions
are avoided. E.g. flavors.
Stability of drug:
• Continuous extraction is avoided for thermo-labile drugs.
• Maceration or percolation methods are preferred.
Cost of drug:
• Expensive drugs (Ginger): complete extraction is preferred.
• Cheap drugs, maceration without size reduction is adequate
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process
Solvent:
• Avoid continuous extraction for solvents other than pure
solvents or azeotropes.
• Used percolation for pure solvents or azeotropes.
Concentration of product:
• Dilute preparations (maceration or percolation)
• Semi-concentrated preparations (efficient percolation or
multiple macerations are used)
• Concentrated preparations (percolation)
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5. Percolation
• It is continuous downward displacement of the
solvent through the bed of crude drug material to
get extract.
• Most frequently used to extract active ingredients
in the preparation of tinctures and fluid extracts.
• It is the method of short successive maceration
or process of displacement.
• A percolator (a narrow, cone-shaped vessel open
at both ends) is generally used.
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Steps in Percolation
1. Size reduction: The drug to be extracted is subjected to
suitable degree of size reduction, usually from coarse
powder to fine powder.
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.
3. Packing: After imbibition the moistened drug is evenly
packed into the percolator.
4. Maceration: After packing sufficient menstruum is added
to saturate the material. The percolator is allowed to
stand for 24 hours to macerate the drug.
5. Percolation: 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.
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Types of Percolation
1.Simple Percolation :
Drug  Imbibition  Maceration  Percolation
• Drug e.g. i) Tincture of Belladonna ii) Compound tincture of
cardamom
2. Modified Percolation :
• Repeated maceration is more effective than simple.
• Multiple maceration – Solvent divided into equal multiple
time considering the solvent retained by plant tissue.
• Used to prepare concentrated preparation.
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Reserved percolation
• In this case the extraction is done through the
general percolation procedure.
• At the last, the evaporation is done under
reduced pressure in equipment like a Climbing
evaporator to the consistency of a soft extract
(semi solid) such that all the water is removed.
• This is then dissolved in the reserved portion
which is strongly alcoholic and easily dissolves
the evaporated portion with any risk of
precipitation.
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Percolation
Merits :
Requires less time than maceration.
Extraction of thermo-labile constituents can
be possible.
Demerits :
Requires more time than soxhalation.
More solvent is required.
Skilled person is required.
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Large scale extraction
• Scale up gradation
From 200ml to 2000L
From 500g to 500Mg
• Economics become very important
Objective is to improve the process efficiency
Solvent amount can be reduced
Reduce the cost of evaporation
Minimize heat damage to thermo-labile
constituents.
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Circulatory Extraction
• Extraction process efficiency is
improved by pumping back the
solvent
• Solvent is sprayed by nozzle
over the drug bed.
• Solvent flow reduced boundary
layers.
• Extraction process will be
incomplete, as solvent flows
through and does not stay to
achieve equilibrium.
• It can be overcome by multiple
stage extraction procedure.
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Spray
nozzle
Drug
Pump
Product

Multiple Stage Extraction
• Drug vessel, circulating pump, spray
distributors and number of tanks are required.
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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 re-charge. 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 re-charge. Repeat cycle.
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Advantages:
• Drug is extracted multiple times (depends
upon no. of receivers)
• Drug is treated with fresh solvent before
discharge, giving maximum extraction.
• The solution is treated with fresh drug before
going for evaporation, giving maximum
chances of extraction.
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Extraction Battery
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Extraction Battery
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Continuous Extraction
• Soxhlet Apparatus
• Continuous hot extraction
• Continuous cold extraction
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Soxhlet Apparatus
Advantages:
 Less solvent is needed.
 Drug is treated continuously with pure solvent.
 Extraction can be continued as long as necessary to
exhaust the drug.
Disadvantages:
Drug must be powdered.
Excessive heat is utilized as solution is boiled
continuously.
Solvent is boiled continuously so the method is
restricted only to pure solvent or azeotropes.
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Extraction_Physical Pharmacy_2nd sem_HAN.pdf

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