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1
EXTRACTION PROCESSES
INTRODUCTION &
DEFINITIONS
2
 Extraction may be defined as the removal of
soluble constituents from a solid or liquid or
semi-solid with means of suitable solvent.
 It may be defined as the treatment of the plant
or animal tissues with appropriate solvent, which
would dissolve the medicinally active
constituents.
 Extraction is the method of removal of a soluble
fraction in the form of a solution from an
insoluble matrix with the help of a suitable
solvent.
• The soluble components may be present either as
 a solid or liquid
• Insoluble matrix may be
 in powder form, openly porous or non porous or cellular
with selective permeable cell walls as in case of vegetable
Example : Boiling tea
3
 Tannins
 Theobromine
 Caffeine
INTRODUCTION &
DEFINITIONS
4
 Extraction involves the separation of medicinally
active portions of plant or animal tissues from the
inactive components through the use of selective
solvents and standard extraction process.
 Menstrum: Solvent used for extraction (ex. water,
alcohol, ether, acetone, ethyl acetate)
 Marc: The inert fibrous and other insoluble materials
remaining after extraction
 Extractives: Concentrated preparations of vegetable
or animal drugs obtained by removal of the active
constituents of the respective drug with suitable
menstrum, evaporation of all or nearly all solvent.
 Tinctures: are alcoholic or hydroalcoholic solutions
prepared from vegetable material or from chemical
substances. E.g. belladona tincture
Menstrum: Polar and non-polar
5
 Polar : water (Di-electric constant: 80), Methanol :
33, Acetone : 21)
 Non-polar : Chloroform (4.81), Hexane (1.88),
Benzene(2.3) , toluene (2.38) , diethyl-ether (4.3),
Solvents with a dielectric constant of less than 15
are generally considered to be non-polar.
INTRODUCTION &
DEFINITIONS
6
 Fluid Extract:
– are liquid preparations of vegetable drugs containing
alcohol as a solvent or as preservative or both.
– Made in such a way that 1ml of extract contains the
therapeutic constituents of 1g of standard drug. E.g.
Cascara sagrada Fluid extract.
 Expression :is a method of fragrance extraction
where raw materials are pressed, squeezed or
compressed and the oils are collected.
 Galanicals: the extract initially obtained by leaching
the vegetable or animal tissue with the suitable
solvent, is converted into concentrated and
converted into a dry extract, a viscous extracts,
liquid extracts. These crude extracts, when
standardized, are known as galenicals.
INTRODUCTION &
DEFINITIONS
7
 Some of the products that are obtained after
extraction process may be summarized as :
• Extraction of fixed oils from seeds.
• Preparation of alkaloid as strychnine from nux-
vomica, quinine from chincona bark.
• Isolation of enzymes as renin and hormones as
insulin from animal sources.
• Extraction of morphine from opium.
• Reserpine from Rauwolfia serpentina.
• Gelatin that is used for making capsule shell is
produced by conversion of skin and bone
collagen by treatment with lime or dilute acid
and is further extracted with warm water.
8
IMPORTANCE OF
EXTRACTION
9
Quantitative description
– Potency of drug can be controlled in
extract than in crude drug and can be used
accordingly.
More Stable form
– Deterioration by enzyme action is
diminished due to separation from bulk.
Enhanced organoleptic characteristic
– more palatable, and more elegant.
IMPORTANCE OF
EXTRACTION
10
Easy formulation
– Tableting of crude material may not be possible.
– Preparation of the drug are more easily
formulated, more stable, palatable and elegant
after extraction
Different route of drug administration
– Injection of crude material may be undesirable and
dangerous
Storage and transport feasibility
– Extracts are less bulky and covers less space
– Smaller bulk facilitates storage and transport.
CLASSIFICATION OF EXTRACTION
11
 Solid-liquid extraction (leaching)
The separation of soluble constituent
from a solid by extraction with a solvent.
it consists of two stages
1. Contact of solute with the liquid phase
2. Separation of the liquid phase from solid
phase
Liquid-liquid extraction
12
• Liquid–liquid extraction, also known
as solvent extraction and partitioning.
• It is a method to separate compounds based on
their relative solubilities in two
different immiscible liquids, usually water and
an organic solvent.
• It is an extraction of a substance from one
liquid phase into another liquid phase.
• is a basic technique-performed using
a separatory funnel.
Liquid-liquid extraction
13
Liquid-liquid extraction is a useful method to separate
components (compounds) of a mixture
RAFFINATE
Liquid-liquid extraction
14
 In this technique, a solvent (known as the
“extractive solvent” ) is brought in contact with
another solvent (termed as the “solute bearing
solvent”) in order to bring about the transfer of one
or more solutes into the first solvent.
 Separation of a substance from a mixture by
preferentially dissolving that substance in a
suitable solvent.
Liquid-liquid extraction
15
• For a given compound, solubility difference
between solvents is quantified as Distribution
Coefficient or partitioning coefficient.
• Distribution Ratio: measure of how well a species
is extracted.
• It is the ratio, K of the solubility of solute
dissolved in the organic layer to the solubility of
material dissolved in the aqueous layer.
• (Note that K is independent of the actual amounts
of the two solvents mixed.)
Liquid-liquid extraction
16
 K= distribution coefficient
 K =solubility in organic (g/100 mL)
solubility in water (g/100 mL)
 The constant K, is essentially the ratio of the
concentrations of the solute in the two different
solvents once the system reaches equilibrium.
 At equilibrium the molecules naturally
distribute themselves in the solvent where they
are more soluble.
 Inorganic and water soluble materials will stay
in the water layer and more organic molecules
will remain in the organic layer.
Liquid-liquid extraction
17
 Unless K is very large, not all of a solute will
reside in the organic layer in a single extraction.
 Usually two, three, or four extractions of the
aqueous layer with an organic solvent are carried
out in sequence in order to remove as much of the
desired product from the aqueous layer as possible.
Liquid-liquid extraction
18
•The greater the
number of small
extractions, the
greater the quantity
of solute removed.
•However for
maximum efficiency
the rule of thumb is
to extract three times
with 1/3 volume
Case 1:
19
 Suppose a particular extraction proceeds with
a distribution coefficient of 10. The system
consists of 5.0g of organic compound
dissolved in 100mL of water (solvent 1). In this
illustration the compare the effectiveness of
three 50mL extractions with
 diethyl ether (aka ether, solvent 2 )with one
150mL extraction with ether.
 Case one: Doing one extraction of 150 mL of
ether. Case two: Doing three extractions of 50
mL of ether each time.
Solvents used for extraction process
20
• The ideal solvent for a certain pharmacologically
active constituent should:
– Be highly selective for the compound to be
extracted.
– Have a high capacity for extraction.
– Not react with the extracted compound or with
other compounds in the plant material.
– Have a low price.
– Be harmless to man and to the environment.
– Be completely volatile.
– The generally used solvents includes: Water,
ether, alcohol, chloroform.
Solvents used for extraction process
21
Disadvantages of water as a solvent
• Most active plant constituents are complex organic
chemical which are less soluble in water.
• Plant constituents such as sugars, gums, starches,
coloring agents, tannins are easily extracted by water
, however are not desirable component sometimes
and may interfere with clarity of the preparation.
• Aqueous preparations serve as excellent growth for
molds, yeasts and bacteria. Preservatives should be
added such as alcohol.
• Water causes hydrolysis of many substances.
• Maximum amount of heat is needed to concentrate
the extraction than non-aqueous solvent.
Solvents used for extraction process
22
Advantages of water as menstruum:
• Readily available
• Cheapness
• Good solvent action for many plant
constituents
• Used with other solvents
Solvents used for extraction process
23
Alcohol:
• Solvent of alkaloids, alkaloidal salts, glycosides,
volatile oils and resins
• Also dissolves many forms of coloring matter,
tannins, many organic acids and salts.
• Alcohol does not dissolve albuminous matter,
gums, waxes, fats, fixed oils and sugars.
Solvents used for extraction process
24
Advantages
• No microbial contamination in alcohol solution
containing 20% or more alcohol concentration.
• A small amount of heat needed to concentrate the
alcoholic preparations
• Non-toxic
• Dissolves selected active constituents of drugs
Disadvantages
• Costly
• Flammable
Solvents used for extraction process
25
 Acetone and chlorinated hydrocarbons may
also be used for leaching purpose.
 More selective solvents used for extraction of
alkaloid are petroleum ether and benzene.
 Potassium hydroxide may be used to extract
eugenol from clove.
Theory of extraction
26
1. Suitable size reduction
2. Penetration of drug by the solvent
3. Solution of the soluble matter within the cells
4. Escape of dissolved material through the cell
walls and through the boundary layer
surrounding the particles
5. Separation of the solution and exhausted drug
Theory of extraction
27
size reduction
 Inorder to achieve proper extraction maximum
surface area of contact would be desirable.
 If the size of drug is reduced to individual cell
size then it would be the best option.
 It is not feasible to reduce the size of material
to cellular level as
• It may cause decomposition of constituents or
may lead to loss of volatile materials.
• Very fine particles may not form good
suspension as they wouldn’t sediment at the
desired rate and particle size if reduced to
cellular level be form sticky mass.
• Dilution of extracts may occur as breakage of
cell may result in release of all cellular content
Theory of extraction
28
The appropriate degree of size reduction will
comply with the following requirements
a. Increased surface area by distortion or
breakage of cells which facilitates penetration
of solvent and escape the soluble matter.
b. Decrease in radial distance will help in setting
up the concentration gradient
Disadvantages of size reduction
a. Slow down the rate of percolation
b. Difficulty in the separation of the insoluble
solid fraction after extraction
c. Poor quality of extract by extracting
undesirable constituents due to breakage of
cell wall which exposes other cellular
materials to solvent action
29
 Degree of size reduction
– Depends upon botanical structure of drugs
• Sliced (for soft drugs like gentian)
• Coarse to Moderately coarse (for cascara,
belladona)
• Moderately fine (for hard and woody drugs like
ipecacuanha)
• Coarse powder for leafy structure
 Appropriate degree of size reduction will result
– Cause some cells to be cracked or distorted
– Particle size that will not result in a very long path
for solvent.
– Particle with large surface area for adequate mass
transfer.
30
Penetration of solvent into the drug
 A drug in dry state is porous due to shrinkage and
pores contain air that must be displaced as the
solvent enters into the pores and penetrates into
the cells.
 When drug is dried, micellae (cellulose in cell wall) loses
its film of water.
 When the drug is moistened the micellae take up a liquid
film and tissue swell
 Swelling continues until the pressure caused by liquid
layer is equal to the cohesive forces between micellae
 Swelling may occur due to
a. Distension of cell wall
b. Bursting of thin walled cell
The solvent must displace air from pores in the
drug.
31
Solubilization of constituents
 When the solvent penetrates in the cells,
dissolution of the constituents takes place and is
governed by surface area, temperature, viscosity.
 The most important factors which will increase the
rate of extraction is elevation of temperature.
Dissolution: Dissolution of a solid in a liquid
involves transfer of molecules or ions (mass)
from a solid state into solution.
32
Escape of solution from the cells
 The dissolved material reaching the surface
of the particle must pass through the
boundary layer at the solid liquid interface.
The rate of diffusion will depend on the
 Presence of suitable concentration
gradient from the centre of the particle,
outwards and through the boundary layer
 Thickness of boundary layer
 Diffusion coefficient of the solute in the
solvent
Theory
33
• This theory suggests that the process of dissolution
of solid particles in a liquid, in absence of reactive
or chemical forces consist of two consecutive
steps:
– Solution of the solid due to interfacial reaction to form
a thin film at the solid/liquid interface called a
stagnant film or diffusion layer which is saturated with
the drug (Cs)
– Diffusion of the soluble solute from the stagnant layer
to the bulk of the solution (Cb)
Noyes’s Whitney equation
34
• The dissolution of drugs from a single spherical particle can be
described by the Noyes’s-Whitney equation which explains the rate
of dissolution when the process is diffusion controlled and involves
no chemical reaction.
• “The rate of mass transfer of solute molecules or ions through
a static diffusion layer is directly proportional to the area
available for molecular/ionic migration and concentration
difference across the boundary layer and is inversely
proportional to the thickness of the boundary layer”
Given as,
dC/dt= DA (Cs-Cb)/h
Where,
dC/dt = is the dissolution rate
D = diffusion coefficient of the solute in solution
S = surface area of the exposed solid
h = thickness of the diffusion layer
Cs = Concentration of solute particle at the boundary layer
Cb = concentration of the solute in the bulk solution
Influence of some parameter on
dissolution rate of drug
35
• Diffusion coefficient (D):Greater the value, faster the
dissolution. Diffusion decreases as the viscosity of
dissolution medium increases.
• Surface area of solid drug (A): Greater the surface
area, faster the dissolution; can be increased by
micronization of drug.
• Concentration gradient (Cs – Cb): Greater the
concentration gradient, faster the diffusion and drug
dissolution: Can be increased by increasing drug
solubility and the volume of dissolution medium.
• Thickness of stagnant layer (h): More the thickness,
lesser the diffusion and drug dissolution; can be
decreased by increasing agitation.
Factor influencing Extraction
36
The rate of extraction can be affected in the
following ways:
I. Where drug immersed in a solvent
a. By agitating the mixture occasionally, local
concentration of the solution is dispersed increasing
the concentration gradient.
b. By agitating the drug and solvent continuously
increases the concentration gradient by dispersion of
local concentration as well as reduces the thickness
of the boundary layer.
c. By suspending the drug in a cloth or above a
perforated plate near the surface of the liquid. As the
drug dissolves, the density of the solution increases
leading to the convection of the solution, increasing
the concentration gradient through the boundary
layers
37
II. If the drug is positioned so that the solvent flows
past the particles
a. The flow replaces the solution by pure solvent
causing the increase in the concentration gradient
b. Flow of the solvent between the particles reduces
the boundary layer increasing the concentration
gradient.
This can be achieved by suspending drug in a cloth bag or
above a perforated plate
III. Elevated temperature’s advantages
a. Solubility of most of the material is higher at
higher temperature.
b. Viscosity of the solvent gets reduced decreasing
boundary layer thickness
c. Diffusion coefficient is proportional to the absolute
temperature and inversely proportional to the
viscosity, so raising the temperature influences the
rate of diffusion considerably.
d. By setting convection current
38
Separation of solution and exhausted
drug
 In the process of immersion of drug in a
bulk of solvent, the solid material has to be
strained off, as the drug absorbs solvent
there is a residue of soluble constituents in
this solvent.
 In this case the drug is subjected to
pressure to expel as much of the solution
as possible.
 Even though the extraction process uses
solvent flowing through the drug, separation
of solution is essential.
PROCESSES USED FOR
EXTRACTION
39
SIMPLE
PERCOLATION
MACERATION
WITH
ADJUSTMENT
SIMPLE
MACERATION
MULTIPLE
MACERATION
PERCOLATION
PROCESS FOR
CONCENTRATED
PREPARATIONS
CONTINIOUS
PERCOLATION
PROCESS
RESERVE
PERCOLATION
PROCESS
MODIFIED
PERCOLATION
PROCESS
EXTRACTION PROCESS
INFUSION DECOCTION MACERATION PERCOLATION DIGESTION
CONCENTRATED
INFUSION
FRESH
INFUSION
40
 Drug : menstrum ratio = 1: 10
INFUSION
41
 Infusion is the process of extracting chemical
compounds or flavors from plant material in a
solvent such as water, oil or alcohol, by allowing
the material to remain suspended in the solvent
over time (a process often called steeping).
 An infusion is also the name for the resultant
liquid.
INFUSION
42
 Infusions are dilute solutions containing the
readily-soluble constituents of crude drugs.
 Formerly, fresh infusions, prepared by
macerating the drug for a short period in cold
water or boiling water were used.
 Now, fresh infusions are usually prepared by
diluting one volume of a concentrated infusion to
ten volumes with water.
 Concentrated infusions are prepared by modified
percolation or maceration process.
 Fresh infusions are liable to fungus and bacterial
growth, and it is necessary to dispense them
within twelve hours of their preparation.
43
 It is used for those drugs which are soft in
nature so that water may penetrate easily to the
tissues and the active constituents are water
soluble.
Procedure used
 It involves pouring water over drugs and
allowing it to keep in contact with water for the
stated period, usually 15 minutes, with
occasional stirring and finally filtering off the
liquid.
 Marc is not pressed
 Boiling water commonly used as solvent
 After the specified time the liquid is filtered and
dispense as drug.
Short time is sufficient for extraction due to
readily soluble constituent of crude drug and its
DECOCTION
44
 This is another process of extraction in which the
water soluble and heat stable constituents of hard
and woody crude drugs are extracted out.
 For extraction of drugs with water soluble and
non- volatile constituents, and drugs of hard and
woody nature.
 Water is used as a solvent and the crude drug
which is to be extracted is cut in to small pieces and
boiled with water for the stated time, usually 10 to 15
minutes.
 Previously sliced drug barks or wood (5 parts) is
boiled with water (100 or 120 parts) in a vessel of
enameled iron or earthenware for a definite length of
time (15 min.) counting from when the liquid starts to
boil with occasional stirring.
DECOCTION
45
 To obtain highly concentrated decoction, boiling
is continued until the liquid reduced to a certain
volume.
 Allow to cool to about 40ºC, press the marc and
mix the resulting liquid to the decoction.
 At the end of decoction time, decoction is
strained through fine muslin.
 Then, sufficient water is passed through the
strainer to produce a definite volume.
Decoction
46
• Example: Cinchona bark
or wood
(contains quinine)
Uses: treatment of fever,
malaria and as an appetite
Stimulant.
Also used in anemia,
indigestion,
gastrointestinal disorders,
general fatigue.
• Tea making is an example of decoction.
Comparison between infusion and decoction
Item Infusion Decoction
1- Plant Soft structure (ex. Senna
leaves)
Hard woody structure (ex.
Cinchona bark)
2- Menstrum Boiling or cold water Boiling water
3- Procedure Infusing the drug with cold or
hot water
Boiling the drug with
water
4- Time Calculated as soon as water is
added to drug
Calculated as soon as the
water begins to boil
5- Adjustment
of final volume
No adjustment Adjustment is necessary
6- Apparatus Infusion earthenware pot Any covered apparatus
7- Storage Used fresh within 12 hours Used fresh and when
stored in refrigerator used
within few days
47
DIGESTION
48
 Digestion is the process in which heat as
well as pressure is used for extraction.
 The equipment is like a pressure cooker or
autoclave and is called digester.
 Extraction of non-thermolabile materials is
more efficient in it because of high
penetration power of solvent and
solubilisation rate of soluble matters of the
crude drug due to high pressure and
temperature respectively
MACERATION
49
Various types of maceration process are
 Simple Maceration: A process for tinctures made
from organized drug e.g. roots, stems, leaves etc.
 Maceration with Adjustment: A process for
tinctures made from unorganized drugs such as
oleo resins and gum resins.
 Double Maceration and Triple Maceration
Process: for concentrated preparations.
Maceration
50
Plant material (crushed or cut
small or moderately coarse
powder)
Placed in a closed vessels
Menstruum added (whole)Allowed to stand for 7 days
shaking occasionally
Liquid strained off Solid residue (marc)pressed
(recover as much as occluded)
(Strained and expressed
liquids mixed)
Clarified by subsidence and
filtration
Evaporation and concentration
SIMPLE MACERATION
51
• Drug is placed in wide mouthed container which
can be well stoppered to prevent the evaporation
of menstruum which is mostly concentrated
alcohol.
• The drug is placed with the whole of the
menstruum in a closed vessel for 7 days
• During this period shaking is done occasionally
• After 7 days liquid is strained and marc is
pressed – in filter press, hydraulic press or hand
press, squeezed in muslin piece etc.
• Then filtered to make a clear liquid.
• The final volume is not adjusted.
• E.g. tincture of orange, tincture of lemon
MACERATION WITH ADJUSTMENT
52
 The unorganized drug is placed with 4/5th of
menstruum in a closed vessel in a closed vessel
for a period of 2-7 days
 Shaking done occasionally
 After the stated period, the liquid is filtered and
the final volume is made up by passing the
remaining 1/5th of the menstruum through the
filter
 The marc is not pressed
 E.g. tincture of tolu, compound tincture of
benzoin
Maceration for organized and
unorganized drug
53
 Organized: Put total menstrum , marc is pressed ,
vol not adjusted
 Unorganized : 4/5 th of the menstrum, marc-not
pressed, vol. adjusted
MULTIPLE MACERATION
54
 Multiple Maceration:-It is established that the
maximum extraction is obtained in multiple
maceration when the total quantity of menstruum
to be used is divided in such a way that same
quantity of menstruum is present during each
maceration.
 Some time this single process of extraction is
not sufficient, then double or triple maceration is
also done, in which the above whole process is
repeated to make the extraction process more
effective. We do not have to change the process
just we have to repeat it for specified times (2-4)
times, all other things is same.
DOUBLE MACERATION
55
 The drug is macerated twice with the
menstruum which is divided into two equal
volume.
Where
 V1 is volume of menstruum required for first
maceration
Vt is total volume of menstruum
Vr is volume of menstruum to be retained by
drug or marc
 Volume required for 2nd maceration is the
difference between Vt and V1
 Vr is determined by performing trial to get
volume retained by known weight of drug
DOUBLE MACERATION
56
 The whole of the drug is macerated for 48 hours
with the quantity of menstruum required for first
maceration.
 Strain the liquid and press the marc.
 Macerate again for 24 hours with the remaining
menstruum required for second maceration
 Strain the liquid and press the marc.
 Mix the liquids obtained from two macerations
and allow it to stand for 14 days and filter.
 E.g. concentrated compound infusion of Chirata,
concentrated compound infusion of Gentian
TRIPLE MACERATION
57
 In this process, the drug is macerated thrice by
using menstruum which is divided into 3 parts in
such a manner that same volume is used for each
maceration.
 Volume of menstruum required by the first maceration=
total vol. of menstruum – vol. to be retained by the drug + Vol. to be retained by drug
3
 Volume of menstruum required by the second
maceration=
Total volume of menstruum - vol. of menstruum used in first maceration
2
TRIPLE MACERATION
58
 The whole of the drug is macerated for 1 hr with
a part of menstruum required for first maceration
and strained.
 Macerate again for 1 hr with a part of menstruum
required for 2nd maceration and strained.
 Macerate again for 1 hr with a part of menstruum
required for 3rd maceration and strained.
 Press marc lightly then combine the liquid
obtained from 2nd and 3rd maceration and
evaporate it to a specific extent
TRIPLE MACERATION
59
 Mix it with the liquid obtained from 1st maceration
 Add alcohol 90% equal to 1/4th of the volume of
the finished product
 Adjust volume with water.
 Allow to stand for 14 days and filter
 E.g. concentrated infusion of Quassia, liquid
 extract of Senna
PERCOLATION
60
1. Simple percolation or percolation process for
tinctures.
2. Percolation processes for concentrated
preparations such as:
i. Reserve percolation process
ii. Modified percolation process
3. Continuous hot percolation or Soxhelation
PERCOLATION – APPARATUS
• Conical percolator
• Cylindrical percolator
• Steam jacketed percolator
PERCOLATION
61
Fig: Simple percolator
SIMPLE PERCOLATION
62
 There are three stages in the official method for
preparation of tinctures by percolation process
 Imbibition:
 powdered drug is moistened with a sufficient quantity of
menstruum and allowed to stand for 4 hours in a closed
vessel.
 It is done inorder to allow swelling of the tissues
before packing into the percolator.
 Dry powder if packed into percolator may cause
blockage of the percolator.
 It allows entrapped air to escape, dry powder drug
would have air entrapped within them, this may resist
the flow of menstrumm and will disturb the packing of
the powdered drug.
SIMPLE PERCOLATION
63
 Prior to packing of the imbibed drug into percolator uniformity
of particle size is ensured by passing the moistened mass
through a sieve of coarse aperture.
 Glass wool moistened with solvent is kept at the bottom to avoid
blockage of outlet or tap. Cotton wool may not be used as after
getting soaked it would also create a impermeable mass.
 The imbibed drug is packed in the percolator upto 2/3rd or 3/4th
of the volume of percolator.
 Filter paper is placed above this layer and above this a layer of
sand is placed inorder to prevent disturbance of top layer when
the menstrumm is added into the percolator.
 Sufficient quantity of menstruum needs to be added to saturate
the material.
 When the liquid starts coming out of the percolator outlet is
closed and add menstrumm forming a layer of solvent above the
imbibed mass.
SIMPLE PERCOLATION
64
 Maceration:
 The moistened drug is left in contact with
menstruum for 24 hrs.
 During this period, menstruum dissolves the
active constituent of the drug and becomes
almost saturated with it.
 Percolation
 It consists of the downward displacement of
the saturated solution formed in maceration
and extraction of the remaining active
constituents present in the drug by the slow
passage of the menstruum through the
column of the drug.
SIMPLE PERCOLATION
65
 After collecting 3/4th of the required volume
of the finished product or when the drug is
completely exhausted, the marc is pressed.
 Mix the expressed liquid with percolate.
 Add sufficient quantity of menstruum to
produce the required volume and then filter.
E.g. tincture of belladona, compound tincture of
cardamom, strong tincture of ginger.
PERCOLATION PROCESS FOR CONCENTRATED
PREPARATIONS
66
 Used to prepare liquid extracts and solid extracts.
 Types of processes are:
 Reserve percolation process
 Modified percolation process
Reserved Percolation Process
67
• In this process, a part of percolate, usually 3/4th of
the volume of the finished preparation, is reserved
(first percolate) containing high solute
concentration.
• Percolation process is continued till the drug is
completely exhausted.
• The percolate thus receives contains traces of active
constituents of the drug.
• Evaporation or distillation is done to recover the
costly menstruum.
• Hence, the major portion of the active constituents
of the drug are saved from detorioration.
• The remaining soft extract is then added to reserve
percolate.
• Volume make up is done using menstruum.
MODIFIED PERCOLATION PROCESS
68
• In percolation process, 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 the displacement process.
• The strong solution of active constituents of drug
formed during maceration is displaced by the fresh
menstruum when percolation process is started.
• Menstruum remaining in contact with the drug dissolves
more matter than the flowing menstruum.
MODIFIED PERCOLATION PROCESS
69
• Hence, more menstruum is required to exhaust the drug when
simple percolation process is used.
• In simple percolation process:
 Drug Imbitition Maceration percolation and collect
the percolate, i.e. ¾ of the volume of the finished product.
In modified percolation process:
Drug-imbibition-maceration-percolation and collect 1000ml of percolate
(24hr)
-maceration-percolation and collect 1000ml of percolate
(12hr)
-maceration –percolation and collect 1000ml of percolate
(12hr)
Drug:percolate
1000gm:3000ml
d/p=1:3
MODIFIED PERCOLATION PROCESS
70
 After exhaustion of the drug, the percolate is
evaporated and then mixed with the main
percolate.
 The final volume is made by adding more of
menstruum.
Continuous hot percolation process or soxhlet
extraction or soxhleation
71
 When active constituents of the drug are not freely
soluble in the solvent or difficult to be displaced
from the cells of the drug, then it becomes necessary
to extract the crude drug by action of hot menstruum
for a considerable length of time.
 The fixed oils from seeds and alkaloids from the
drug are extracted by continuous hot percolation
process using benzene, chloroform, petroleum, ether
etc.
Soxhlet apparatus
72
1. Flask containing the boiling water
2. Soxhlet Extractor: in which the drug to be extracted
is packed.
 It has a side tube which carries the vapors of the solvent
from the flask to the condenser and a siphon tube which
siphons over the extract from soxhlet extractor to the
flask.
 A condenser in which the vapors of the solvent are
condensed again into solvent.
Soxhlet apparatus
73
Soxhlation
74
PROCEDURE
 The drug is packed in a paper cylinder made from a filter
paper and it is placed in the body of soxhlet extractor.
 The solvent is placed in the flask
 The apparatus is then fitted as shown is figure.
 When solvent is boiled on heating flask, it gets
converted into vapors.
 These vapors enter into the condenser through the side
tube and get condensed into hot liquid which falls on
column of the drug.
 When the extractor gets filled with the solvent, the level
of siphon tube also raises up to its top.
Soxhlation
75
 The solvent containing active constituents in the
siphon tube siphon over and run into the flask, thus
emptying the body of extractor.
 This alteration of filling and emptying the body of
extractor goes on continuously until the drug is
exhausted (normally 15 times).
 The soluble active constituent of the drug remain
in the flask where solvent is repeatedly volatilized.
Factors affecting the choice of extraction
process
76
1. Character of drug
• Knowledge of pharmacognosy – maceration process if
drug is soft, percolation process used when drug is
hard and tough
2. Therapeutic value of the drug:
• when the drug has high therapeutic value, maximum
extraction is required, so percolation process is used
e.g. Belladona.
3. Cost of drug
• costly drugs are extracted by percolation process,
whereas cheap drugs are extracted by maceration
process.
Factors affecting the choice of extraction
process
77
4. Stability of drug:
 Thermolabile drugs-maceration or percolation
should be done.
 No hot extraction process should be carried out.
5. solvent:
 Maceration process recommended-if water is
used as solvent.
 Percolation process-nonaqueous solvents.
Factors affecting the choice of extraction
process
78
6. Concentration of product –
• The dilute products such as tinctures can be
made by using maceration or percolation
process, depending on other factors.
• For semi-concentrated preparations, such as
concentrated infusions, double or triple
maceration process can be used.
• The liquid extracts or dry extracts or dry extracts
which are concentrated preparations are prepared
by using percolation process.
References
79
 Tutorial Pharmacy by cooper and guns.
 Pharmaceutics I by Mehta

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Extraction Processes Explained

  • 2. INTRODUCTION & DEFINITIONS 2  Extraction may be defined as the removal of soluble constituents from a solid or liquid or semi-solid with means of suitable solvent.  It may be defined as the treatment of the plant or animal tissues with appropriate solvent, which would dissolve the medicinally active constituents.  Extraction is the method of removal of a soluble fraction in the form of a solution from an insoluble matrix with the help of a suitable solvent. • The soluble components may be present either as  a solid or liquid • Insoluble matrix may be  in powder form, openly porous or non porous or cellular with selective permeable cell walls as in case of vegetable
  • 3. Example : Boiling tea 3  Tannins  Theobromine  Caffeine
  • 4. INTRODUCTION & DEFINITIONS 4  Extraction involves the separation of medicinally active portions of plant or animal tissues from the inactive components through the use of selective solvents and standard extraction process.  Menstrum: Solvent used for extraction (ex. water, alcohol, ether, acetone, ethyl acetate)  Marc: The inert fibrous and other insoluble materials remaining after extraction  Extractives: Concentrated preparations of vegetable or animal drugs obtained by removal of the active constituents of the respective drug with suitable menstrum, evaporation of all or nearly all solvent.  Tinctures: are alcoholic or hydroalcoholic solutions prepared from vegetable material or from chemical substances. E.g. belladona tincture
  • 5. Menstrum: Polar and non-polar 5  Polar : water (Di-electric constant: 80), Methanol : 33, Acetone : 21)  Non-polar : Chloroform (4.81), Hexane (1.88), Benzene(2.3) , toluene (2.38) , diethyl-ether (4.3), Solvents with a dielectric constant of less than 15 are generally considered to be non-polar.
  • 6. INTRODUCTION & DEFINITIONS 6  Fluid Extract: – are liquid preparations of vegetable drugs containing alcohol as a solvent or as preservative or both. – Made in such a way that 1ml of extract contains the therapeutic constituents of 1g of standard drug. E.g. Cascara sagrada Fluid extract.  Expression :is a method of fragrance extraction where raw materials are pressed, squeezed or compressed and the oils are collected.  Galanicals: the extract initially obtained by leaching the vegetable or animal tissue with the suitable solvent, is converted into concentrated and converted into a dry extract, a viscous extracts, liquid extracts. These crude extracts, when standardized, are known as galenicals.
  • 7. INTRODUCTION & DEFINITIONS 7  Some of the products that are obtained after extraction process may be summarized as : • Extraction of fixed oils from seeds. • Preparation of alkaloid as strychnine from nux- vomica, quinine from chincona bark. • Isolation of enzymes as renin and hormones as insulin from animal sources. • Extraction of morphine from opium. • Reserpine from Rauwolfia serpentina. • Gelatin that is used for making capsule shell is produced by conversion of skin and bone collagen by treatment with lime or dilute acid and is further extracted with warm water.
  • 8. 8
  • 9. IMPORTANCE OF EXTRACTION 9 Quantitative description – Potency of drug can be controlled in extract than in crude drug and can be used accordingly. More Stable form – Deterioration by enzyme action is diminished due to separation from bulk. Enhanced organoleptic characteristic – more palatable, and more elegant.
  • 10. IMPORTANCE OF EXTRACTION 10 Easy formulation – Tableting of crude material may not be possible. – Preparation of the drug are more easily formulated, more stable, palatable and elegant after extraction Different route of drug administration – Injection of crude material may be undesirable and dangerous Storage and transport feasibility – Extracts are less bulky and covers less space – Smaller bulk facilitates storage and transport.
  • 11. CLASSIFICATION OF EXTRACTION 11  Solid-liquid extraction (leaching) The separation of soluble constituent from a solid by extraction with a solvent. it consists of two stages 1. Contact of solute with the liquid phase 2. Separation of the liquid phase from solid phase
  • 12. Liquid-liquid extraction 12 • Liquid–liquid extraction, also known as solvent extraction and partitioning. • It is a method to separate compounds based on their relative solubilities in two different immiscible liquids, usually water and an organic solvent. • It is an extraction of a substance from one liquid phase into another liquid phase. • is a basic technique-performed using a separatory funnel.
  • 13. Liquid-liquid extraction 13 Liquid-liquid extraction is a useful method to separate components (compounds) of a mixture RAFFINATE
  • 14. Liquid-liquid extraction 14  In this technique, a solvent (known as the “extractive solvent” ) is brought in contact with another solvent (termed as the “solute bearing solvent”) in order to bring about the transfer of one or more solutes into the first solvent.  Separation of a substance from a mixture by preferentially dissolving that substance in a suitable solvent.
  • 15. Liquid-liquid extraction 15 • For a given compound, solubility difference between solvents is quantified as Distribution Coefficient or partitioning coefficient. • Distribution Ratio: measure of how well a species is extracted. • It is the ratio, K of the solubility of solute dissolved in the organic layer to the solubility of material dissolved in the aqueous layer. • (Note that K is independent of the actual amounts of the two solvents mixed.)
  • 16. Liquid-liquid extraction 16  K= distribution coefficient  K =solubility in organic (g/100 mL) solubility in water (g/100 mL)  The constant K, is essentially the ratio of the concentrations of the solute in the two different solvents once the system reaches equilibrium.  At equilibrium the molecules naturally distribute themselves in the solvent where they are more soluble.  Inorganic and water soluble materials will stay in the water layer and more organic molecules will remain in the organic layer.
  • 17. Liquid-liquid extraction 17  Unless K is very large, not all of a solute will reside in the organic layer in a single extraction.  Usually two, three, or four extractions of the aqueous layer with an organic solvent are carried out in sequence in order to remove as much of the desired product from the aqueous layer as possible.
  • 18. Liquid-liquid extraction 18 •The greater the number of small extractions, the greater the quantity of solute removed. •However for maximum efficiency the rule of thumb is to extract three times with 1/3 volume
  • 19. Case 1: 19  Suppose a particular extraction proceeds with a distribution coefficient of 10. The system consists of 5.0g of organic compound dissolved in 100mL of water (solvent 1). In this illustration the compare the effectiveness of three 50mL extractions with  diethyl ether (aka ether, solvent 2 )with one 150mL extraction with ether.  Case one: Doing one extraction of 150 mL of ether. Case two: Doing three extractions of 50 mL of ether each time.
  • 20. Solvents used for extraction process 20 • The ideal solvent for a certain pharmacologically active constituent should: – Be highly selective for the compound to be extracted. – Have a high capacity for extraction. – Not react with the extracted compound or with other compounds in the plant material. – Have a low price. – Be harmless to man and to the environment. – Be completely volatile. – The generally used solvents includes: Water, ether, alcohol, chloroform.
  • 21. Solvents used for extraction process 21 Disadvantages of water as a solvent • Most active plant constituents are complex organic chemical which are less soluble in water. • Plant constituents such as sugars, gums, starches, coloring agents, tannins are easily extracted by water , however are not desirable component sometimes and may interfere with clarity of the preparation. • Aqueous preparations serve as excellent growth for molds, yeasts and bacteria. Preservatives should be added such as alcohol. • Water causes hydrolysis of many substances. • Maximum amount of heat is needed to concentrate the extraction than non-aqueous solvent.
  • 22. Solvents used for extraction process 22 Advantages of water as menstruum: • Readily available • Cheapness • Good solvent action for many plant constituents • Used with other solvents
  • 23. Solvents used for extraction process 23 Alcohol: • Solvent of alkaloids, alkaloidal salts, glycosides, volatile oils and resins • Also dissolves many forms of coloring matter, tannins, many organic acids and salts. • Alcohol does not dissolve albuminous matter, gums, waxes, fats, fixed oils and sugars.
  • 24. Solvents used for extraction process 24 Advantages • No microbial contamination in alcohol solution containing 20% or more alcohol concentration. • A small amount of heat needed to concentrate the alcoholic preparations • Non-toxic • Dissolves selected active constituents of drugs Disadvantages • Costly • Flammable
  • 25. Solvents used for extraction process 25  Acetone and chlorinated hydrocarbons may also be used for leaching purpose.  More selective solvents used for extraction of alkaloid are petroleum ether and benzene.  Potassium hydroxide may be used to extract eugenol from clove.
  • 26. Theory of extraction 26 1. Suitable size reduction 2. Penetration of drug by the solvent 3. Solution of the soluble matter within the cells 4. Escape of dissolved material through the cell walls and through the boundary layer surrounding the particles 5. Separation of the solution and exhausted drug
  • 27. Theory of extraction 27 size reduction  Inorder to achieve proper extraction maximum surface area of contact would be desirable.  If the size of drug is reduced to individual cell size then it would be the best option.  It is not feasible to reduce the size of material to cellular level as • It may cause decomposition of constituents or may lead to loss of volatile materials. • Very fine particles may not form good suspension as they wouldn’t sediment at the desired rate and particle size if reduced to cellular level be form sticky mass. • Dilution of extracts may occur as breakage of cell may result in release of all cellular content
  • 28. Theory of extraction 28 The appropriate degree of size reduction will comply with the following requirements a. Increased surface area by distortion or breakage of cells which facilitates penetration of solvent and escape the soluble matter. b. Decrease in radial distance will help in setting up the concentration gradient Disadvantages of size reduction a. Slow down the rate of percolation b. Difficulty in the separation of the insoluble solid fraction after extraction c. Poor quality of extract by extracting undesirable constituents due to breakage of cell wall which exposes other cellular materials to solvent action
  • 29. 29  Degree of size reduction – Depends upon botanical structure of drugs • Sliced (for soft drugs like gentian) • Coarse to Moderately coarse (for cascara, belladona) • Moderately fine (for hard and woody drugs like ipecacuanha) • Coarse powder for leafy structure  Appropriate degree of size reduction will result – Cause some cells to be cracked or distorted – Particle size that will not result in a very long path for solvent. – Particle with large surface area for adequate mass transfer.
  • 30. 30 Penetration of solvent into the drug  A drug in dry state is porous due to shrinkage and pores contain air that must be displaced as the solvent enters into the pores and penetrates into the cells.  When drug is dried, micellae (cellulose in cell wall) loses its film of water.  When the drug is moistened the micellae take up a liquid film and tissue swell  Swelling continues until the pressure caused by liquid layer is equal to the cohesive forces between micellae  Swelling may occur due to a. Distension of cell wall b. Bursting of thin walled cell The solvent must displace air from pores in the drug.
  • 31. 31 Solubilization of constituents  When the solvent penetrates in the cells, dissolution of the constituents takes place and is governed by surface area, temperature, viscosity.  The most important factors which will increase the rate of extraction is elevation of temperature. Dissolution: Dissolution of a solid in a liquid involves transfer of molecules or ions (mass) from a solid state into solution.
  • 32. 32 Escape of solution from the cells  The dissolved material reaching the surface of the particle must pass through the boundary layer at the solid liquid interface. The rate of diffusion will depend on the  Presence of suitable concentration gradient from the centre of the particle, outwards and through the boundary layer  Thickness of boundary layer  Diffusion coefficient of the solute in the solvent
  • 33. Theory 33 • This theory suggests that the process of dissolution of solid particles in a liquid, in absence of reactive or chemical forces consist of two consecutive steps: – Solution of the solid due to interfacial reaction to form a thin film at the solid/liquid interface called a stagnant film or diffusion layer which is saturated with the drug (Cs) – Diffusion of the soluble solute from the stagnant layer to the bulk of the solution (Cb)
  • 34. Noyes’s Whitney equation 34 • The dissolution of drugs from a single spherical particle can be described by the Noyes’s-Whitney equation which explains the rate of dissolution when the process is diffusion controlled and involves no chemical reaction. • “The rate of mass transfer of solute molecules or ions through a static diffusion layer is directly proportional to the area available for molecular/ionic migration and concentration difference across the boundary layer and is inversely proportional to the thickness of the boundary layer” Given as, dC/dt= DA (Cs-Cb)/h Where, dC/dt = is the dissolution rate D = diffusion coefficient of the solute in solution S = surface area of the exposed solid h = thickness of the diffusion layer Cs = Concentration of solute particle at the boundary layer Cb = concentration of the solute in the bulk solution
  • 35. Influence of some parameter on dissolution rate of drug 35 • Diffusion coefficient (D):Greater the value, faster the dissolution. Diffusion decreases as the viscosity of dissolution medium increases. • Surface area of solid drug (A): Greater the surface area, faster the dissolution; can be increased by micronization of drug. • Concentration gradient (Cs – Cb): Greater the concentration gradient, faster the diffusion and drug dissolution: Can be increased by increasing drug solubility and the volume of dissolution medium. • Thickness of stagnant layer (h): More the thickness, lesser the diffusion and drug dissolution; can be decreased by increasing agitation.
  • 36. Factor influencing Extraction 36 The rate of extraction can be affected in the following ways: I. Where drug immersed in a solvent a. By agitating the mixture occasionally, local concentration of the solution is dispersed increasing the concentration gradient. b. By agitating the drug and solvent continuously increases the concentration gradient by dispersion of local concentration as well as reduces the thickness of the boundary layer. c. By suspending the drug in a cloth or above a perforated plate near the surface of the liquid. As the drug dissolves, the density of the solution increases leading to the convection of the solution, increasing the concentration gradient through the boundary layers
  • 37. 37 II. If the drug is positioned so that the solvent flows past the particles a. The flow replaces the solution by pure solvent causing the increase in the concentration gradient b. Flow of the solvent between the particles reduces the boundary layer increasing the concentration gradient. This can be achieved by suspending drug in a cloth bag or above a perforated plate III. Elevated temperature’s advantages a. Solubility of most of the material is higher at higher temperature. b. Viscosity of the solvent gets reduced decreasing boundary layer thickness c. Diffusion coefficient is proportional to the absolute temperature and inversely proportional to the viscosity, so raising the temperature influences the rate of diffusion considerably. d. By setting convection current
  • 38. 38 Separation of solution and exhausted drug  In the process of immersion of drug in a bulk of solvent, the solid material has to be strained off, as the drug absorbs solvent there is a residue of soluble constituents in this solvent.  In this case the drug is subjected to pressure to expel as much of the solution as possible.  Even though the extraction process uses solvent flowing through the drug, separation of solution is essential.
  • 39. PROCESSES USED FOR EXTRACTION 39 SIMPLE PERCOLATION MACERATION WITH ADJUSTMENT SIMPLE MACERATION MULTIPLE MACERATION PERCOLATION PROCESS FOR CONCENTRATED PREPARATIONS CONTINIOUS PERCOLATION PROCESS RESERVE PERCOLATION PROCESS MODIFIED PERCOLATION PROCESS EXTRACTION PROCESS INFUSION DECOCTION MACERATION PERCOLATION DIGESTION CONCENTRATED INFUSION FRESH INFUSION
  • 40. 40  Drug : menstrum ratio = 1: 10
  • 41. INFUSION 41  Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping).  An infusion is also the name for the resultant liquid.
  • 42. INFUSION 42  Infusions are dilute solutions containing the readily-soluble constituents of crude drugs.  Formerly, fresh infusions, prepared by macerating the drug for a short period in cold water or boiling water were used.  Now, fresh infusions are usually prepared by diluting one volume of a concentrated infusion to ten volumes with water.  Concentrated infusions are prepared by modified percolation or maceration process.  Fresh infusions are liable to fungus and bacterial growth, and it is necessary to dispense them within twelve hours of their preparation.
  • 43. 43  It is used for those drugs which are soft in nature so that water may penetrate easily to the tissues and the active constituents are water soluble. Procedure used  It involves pouring water over drugs and allowing it to keep in contact with water for the stated period, usually 15 minutes, with occasional stirring and finally filtering off the liquid.  Marc is not pressed  Boiling water commonly used as solvent  After the specified time the liquid is filtered and dispense as drug. Short time is sufficient for extraction due to readily soluble constituent of crude drug and its
  • 44. DECOCTION 44  This is another process of extraction in which the water soluble and heat stable constituents of hard and woody crude drugs are extracted out.  For extraction of drugs with water soluble and non- volatile constituents, and drugs of hard and woody nature.  Water is used as a solvent and the crude drug which is to be extracted is cut in to small pieces and boiled with water for the stated time, usually 10 to 15 minutes.  Previously sliced drug barks or wood (5 parts) is boiled with water (100 or 120 parts) in a vessel of enameled iron or earthenware for a definite length of time (15 min.) counting from when the liquid starts to boil with occasional stirring.
  • 45. DECOCTION 45  To obtain highly concentrated decoction, boiling is continued until the liquid reduced to a certain volume.  Allow to cool to about 40ºC, press the marc and mix the resulting liquid to the decoction.  At the end of decoction time, decoction is strained through fine muslin.  Then, sufficient water is passed through the strainer to produce a definite volume.
  • 46. Decoction 46 • Example: Cinchona bark or wood (contains quinine) Uses: treatment of fever, malaria and as an appetite Stimulant. Also used in anemia, indigestion, gastrointestinal disorders, general fatigue. • Tea making is an example of decoction.
  • 47. Comparison between infusion and decoction Item Infusion Decoction 1- Plant Soft structure (ex. Senna leaves) Hard woody structure (ex. Cinchona bark) 2- Menstrum Boiling or cold water Boiling water 3- Procedure Infusing the drug with cold or hot water Boiling the drug with water 4- Time Calculated as soon as water is added to drug Calculated as soon as the water begins to boil 5- Adjustment of final volume No adjustment Adjustment is necessary 6- Apparatus Infusion earthenware pot Any covered apparatus 7- Storage Used fresh within 12 hours Used fresh and when stored in refrigerator used within few days 47
  • 48. DIGESTION 48  Digestion is the process in which heat as well as pressure is used for extraction.  The equipment is like a pressure cooker or autoclave and is called digester.  Extraction of non-thermolabile materials is more efficient in it because of high penetration power of solvent and solubilisation rate of soluble matters of the crude drug due to high pressure and temperature respectively
  • 49. MACERATION 49 Various types of maceration process are  Simple Maceration: A process for tinctures made from organized drug e.g. roots, stems, leaves etc.  Maceration with Adjustment: A process for tinctures made from unorganized drugs such as oleo resins and gum resins.  Double Maceration and Triple Maceration Process: for concentrated preparations.
  • 50. Maceration 50 Plant material (crushed or cut small or moderately coarse powder) Placed in a closed vessels Menstruum added (whole)Allowed to stand for 7 days shaking occasionally Liquid strained off Solid residue (marc)pressed (recover as much as occluded) (Strained and expressed liquids mixed) Clarified by subsidence and filtration Evaporation and concentration
  • 51. SIMPLE MACERATION 51 • Drug is placed in wide mouthed container which can be well stoppered to prevent the evaporation of menstruum which is mostly concentrated alcohol. • The drug is placed with the whole of the menstruum in a closed vessel for 7 days • During this period shaking is done occasionally • After 7 days liquid is strained and marc is pressed – in filter press, hydraulic press or hand press, squeezed in muslin piece etc. • Then filtered to make a clear liquid. • The final volume is not adjusted. • E.g. tincture of orange, tincture of lemon
  • 52. MACERATION WITH ADJUSTMENT 52  The unorganized drug is placed with 4/5th of menstruum in a closed vessel in a closed vessel for a period of 2-7 days  Shaking done occasionally  After the stated period, the liquid is filtered and the final volume is made up by passing the remaining 1/5th of the menstruum through the filter  The marc is not pressed  E.g. tincture of tolu, compound tincture of benzoin
  • 53. Maceration for organized and unorganized drug 53  Organized: Put total menstrum , marc is pressed , vol not adjusted  Unorganized : 4/5 th of the menstrum, marc-not pressed, vol. adjusted
  • 54. MULTIPLE MACERATION 54  Multiple Maceration:-It is established that the maximum extraction is obtained in multiple maceration when the total quantity of menstruum to be used is divided in such a way that same quantity of menstruum is present during each maceration.  Some time this single process of extraction is not sufficient, then double or triple maceration is also done, in which the above whole process is repeated to make the extraction process more effective. We do not have to change the process just we have to repeat it for specified times (2-4) times, all other things is same.
  • 55. DOUBLE MACERATION 55  The drug is macerated twice with the menstruum which is divided into two equal volume. Where  V1 is volume of menstruum required for first maceration Vt is total volume of menstruum Vr is volume of menstruum to be retained by drug or marc  Volume required for 2nd maceration is the difference between Vt and V1  Vr is determined by performing trial to get volume retained by known weight of drug
  • 56. DOUBLE MACERATION 56  The whole of the drug is macerated for 48 hours with the quantity of menstruum required for first maceration.  Strain the liquid and press the marc.  Macerate again for 24 hours with the remaining menstruum required for second maceration  Strain the liquid and press the marc.  Mix the liquids obtained from two macerations and allow it to stand for 14 days and filter.  E.g. concentrated compound infusion of Chirata, concentrated compound infusion of Gentian
  • 57. TRIPLE MACERATION 57  In this process, the drug is macerated thrice by using menstruum which is divided into 3 parts in such a manner that same volume is used for each maceration.  Volume of menstruum required by the first maceration= total vol. of menstruum – vol. to be retained by the drug + Vol. to be retained by drug 3  Volume of menstruum required by the second maceration= Total volume of menstruum - vol. of menstruum used in first maceration 2
  • 58. TRIPLE MACERATION 58  The whole of the drug is macerated for 1 hr with a part of menstruum required for first maceration and strained.  Macerate again for 1 hr with a part of menstruum required for 2nd maceration and strained.  Macerate again for 1 hr with a part of menstruum required for 3rd maceration and strained.  Press marc lightly then combine the liquid obtained from 2nd and 3rd maceration and evaporate it to a specific extent
  • 59. TRIPLE MACERATION 59  Mix it with the liquid obtained from 1st maceration  Add alcohol 90% equal to 1/4th of the volume of the finished product  Adjust volume with water.  Allow to stand for 14 days and filter  E.g. concentrated infusion of Quassia, liquid  extract of Senna
  • 60. PERCOLATION 60 1. Simple percolation or percolation process for tinctures. 2. Percolation processes for concentrated preparations such as: i. Reserve percolation process ii. Modified percolation process 3. Continuous hot percolation or Soxhelation PERCOLATION – APPARATUS • Conical percolator • Cylindrical percolator • Steam jacketed percolator
  • 62. SIMPLE PERCOLATION 62  There are three stages in the official method for preparation of tinctures by percolation process  Imbibition:  powdered drug is moistened with a sufficient quantity of menstruum and allowed to stand for 4 hours in a closed vessel.  It is done inorder to allow swelling of the tissues before packing into the percolator.  Dry powder if packed into percolator may cause blockage of the percolator.  It allows entrapped air to escape, dry powder drug would have air entrapped within them, this may resist the flow of menstrumm and will disturb the packing of the powdered drug.
  • 63. SIMPLE PERCOLATION 63  Prior to packing of the imbibed drug into percolator uniformity of particle size is ensured by passing the moistened mass through a sieve of coarse aperture.  Glass wool moistened with solvent is kept at the bottom to avoid blockage of outlet or tap. Cotton wool may not be used as after getting soaked it would also create a impermeable mass.  The imbibed drug is packed in the percolator upto 2/3rd or 3/4th of the volume of percolator.  Filter paper is placed above this layer and above this a layer of sand is placed inorder to prevent disturbance of top layer when the menstrumm is added into the percolator.  Sufficient quantity of menstruum needs to be added to saturate the material.  When the liquid starts coming out of the percolator outlet is closed and add menstrumm forming a layer of solvent above the imbibed mass.
  • 64. SIMPLE PERCOLATION 64  Maceration:  The moistened drug is left in contact with menstruum for 24 hrs.  During this period, menstruum dissolves the active constituent of the drug and becomes almost saturated with it.  Percolation  It consists of the downward displacement of the saturated solution formed in maceration and extraction of the remaining active constituents present in the drug by the slow passage of the menstruum through the column of the drug.
  • 65. SIMPLE PERCOLATION 65  After collecting 3/4th of the required volume of the finished product or when the drug is completely exhausted, the marc is pressed.  Mix the expressed liquid with percolate.  Add sufficient quantity of menstruum to produce the required volume and then filter. E.g. tincture of belladona, compound tincture of cardamom, strong tincture of ginger.
  • 66. PERCOLATION PROCESS FOR CONCENTRATED PREPARATIONS 66  Used to prepare liquid extracts and solid extracts.  Types of processes are:  Reserve percolation process  Modified percolation process
  • 67. Reserved Percolation Process 67 • In this process, a part of percolate, usually 3/4th of the volume of the finished preparation, is reserved (first percolate) containing high solute concentration. • Percolation process is continued till the drug is completely exhausted. • The percolate thus receives contains traces of active constituents of the drug. • Evaporation or distillation is done to recover the costly menstruum. • Hence, the major portion of the active constituents of the drug are saved from detorioration. • The remaining soft extract is then added to reserve percolate. • Volume make up is done using menstruum.
  • 68. MODIFIED PERCOLATION PROCESS 68 • In percolation process, 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 the displacement process. • The strong solution of active constituents of drug formed during maceration is displaced by the fresh menstruum when percolation process is started. • Menstruum remaining in contact with the drug dissolves more matter than the flowing menstruum.
  • 69. MODIFIED PERCOLATION PROCESS 69 • Hence, more menstruum is required to exhaust the drug when simple percolation process is used. • In simple percolation process:  Drug Imbitition Maceration percolation and collect the percolate, i.e. ¾ of the volume of the finished product. In modified percolation process: Drug-imbibition-maceration-percolation and collect 1000ml of percolate (24hr) -maceration-percolation and collect 1000ml of percolate (12hr) -maceration –percolation and collect 1000ml of percolate (12hr) Drug:percolate 1000gm:3000ml d/p=1:3
  • 70. MODIFIED PERCOLATION PROCESS 70  After exhaustion of the drug, the percolate is evaporated and then mixed with the main percolate.  The final volume is made by adding more of menstruum.
  • 71. Continuous hot percolation process or soxhlet extraction or soxhleation 71  When active constituents of the drug are not freely soluble in the solvent or difficult to be displaced from the cells of the drug, then it becomes necessary to extract the crude drug by action of hot menstruum for a considerable length of time.  The fixed oils from seeds and alkaloids from the drug are extracted by continuous hot percolation process using benzene, chloroform, petroleum, ether etc.
  • 72. Soxhlet apparatus 72 1. Flask containing the boiling water 2. Soxhlet Extractor: in which the drug to be extracted is packed.  It has a side tube which carries the vapors of the solvent from the flask to the condenser and a siphon tube which siphons over the extract from soxhlet extractor to the flask.  A condenser in which the vapors of the solvent are condensed again into solvent.
  • 74. Soxhlation 74 PROCEDURE  The drug is packed in a paper cylinder made from a filter paper and it is placed in the body of soxhlet extractor.  The solvent is placed in the flask  The apparatus is then fitted as shown is figure.  When solvent is boiled on heating flask, it gets converted into vapors.  These vapors enter into the condenser through the side tube and get condensed into hot liquid which falls on column of the drug.  When the extractor gets filled with the solvent, the level of siphon tube also raises up to its top.
  • 75. Soxhlation 75  The solvent containing active constituents in the siphon tube siphon over and run into the flask, thus emptying the body of extractor.  This alteration of filling and emptying the body of extractor goes on continuously until the drug is exhausted (normally 15 times).  The soluble active constituent of the drug remain in the flask where solvent is repeatedly volatilized.
  • 76. Factors affecting the choice of extraction process 76 1. Character of drug • Knowledge of pharmacognosy – maceration process if drug is soft, percolation process used when drug is hard and tough 2. Therapeutic value of the drug: • when the drug has high therapeutic value, maximum extraction is required, so percolation process is used e.g. Belladona. 3. Cost of drug • costly drugs are extracted by percolation process, whereas cheap drugs are extracted by maceration process.
  • 77. Factors affecting the choice of extraction process 77 4. Stability of drug:  Thermolabile drugs-maceration or percolation should be done.  No hot extraction process should be carried out. 5. solvent:  Maceration process recommended-if water is used as solvent.  Percolation process-nonaqueous solvents.
  • 78. Factors affecting the choice of extraction process 78 6. Concentration of product – • The dilute products such as tinctures can be made by using maceration or percolation process, depending on other factors. • For semi-concentrated preparations, such as concentrated infusions, double or triple maceration process can be used. • The liquid extracts or dry extracts or dry extracts which are concentrated preparations are prepared by using percolation process.
  • 79. References 79  Tutorial Pharmacy by cooper and guns.  Pharmaceutics I by Mehta