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Syllabus:         Principles and Equipment used in the following extraction processes:-                  Infusion, Decoction, Expression, Maceration, Percolation.
 


Extraction:
extraction involves the separation of medicinally active portions of plant or animal tissues from the inactive or inert components by using selective solvents in standard extraction procedures.
Discussion:
Belladonna extract is obtained from the leaves of the plant Atropa belladonna. The active ingredient is atropine. Besides atropine starch, lignin, pigments etc. are also present. So to extract the atropine from the leaves a selective solvent has to be used so that only atropine is soluble in it. Thus the active ingredient can be separated from the plant.
Source of drugs (active ingredients) may be plant or animal.
Plant source:              Emetine from Ipecac root, reserpine from Rauwolfia                                               serpentina root, atropine from Belladonna leaves.
Animal source:           Cochineal from insect Coccus cacti.
General procedures:
In this discussion we are concerned primarily with basic extraction procedures for crude drugs to obtain the therapeutically desirable portion and eliminate the inert crude material by treatment with a selective solvent, known as the menstruum.
Let us take some dried leaves (known as the crude drug) in a container, add water in it. The active ingredient will come out in the water. Here water, i.e. the solvent of extraction is called menstruum. Later the water is filtered. The filtrate is known as the extract. The damp crude drugs (damp leaves) are called marc. This marc can be expressed i.e., pressed in a chamber to get the residual liquid, which is mixed with the previous extract.
EXTRACTION PROCESSES
 


INFUSION      DECOCTION      MACERATION      PERCOLATION      DIGESTION
 


Fresh               Concentrated
Infusion           Infusion
 


Simple            Maceration with         Multiple
Maceration     adjustment                  Maceration
                                                                                    Simple            Continuous     Percolation
                        Double                                    Triple              Percolation     Percolation     Process for
                        Maceration                 Maceration                             (Soxhlation)    Conc. Prepns.
 


                                                                                                Reserved                     Modified
                                                                                                Percolation                 Percolation
Extraction procedures:
There are several procedures for extraction: e.g maceration, percolation, digestion, infusion, decoction, digestion etc. Most pharmacopoeias generally refer to maceration and percolation for the extraction of active principles from crude drugs.

MACERATION
Principle:
In this process solid ingredients are placed in a stoppered container with the whole of the solvent and allowed to stand for a period of at least 3 days (3 - 7 days) with frequent agitation, until soluble matter is dissolved. The mixture is then strained (through sieves / nets), the marc pressed and the combined liquids clarified (cleaned by filtration) or by decantation, after standing.

N.B.
Stoppered container is generally taken to reduce the loss of solvents by evaporation. If the volume of solvent is reduced by evaporation then the extract may become concentrated, which may not be desired.
The drug is allowed to stand for few days
i)       to help the solvent to penetrate the cells of the drugs,
ii)     to provide the time for partitioning the active ingredient into the solvent and
iii)   to transfer the drug out of the cells into the bulk of the solvent.
Frequent agitation is required to reduce the localized concentration around the cells and tissues.
As indicated in the pharmacopoeia the process consists of the following:
·       Placing the solid materials with whole menstruum in the closed vessel and allowed to stand for 7 days shaking occasionally.
·       Strained, pressed the marc and the liquid is obtained.
·       Liquid (i.e the extract) is clarified by subsidence or filtration.
The process is normally used for the preparation of tinctures or extracts and menstruum is usually alcoholic, hydroalcoholic (in case of tinctures) or may be aqueous.

1.     Simple maceration - a process for tinctures made from organized drugs e.g. roots, stems, leaves etc.
2.     Maceration with adjustment - a process for tinctures made from unorganized drugs such as oleo-resins and gum resins.
3.     Multiple maceration - a process to prepare concentrated extract. It includes ‘Double maceration’ and ‘Triple maceration’.
SIMPLE MACERATION
Organized drugs having specific cell structures like roots, stems, leaves, flowers etc. are extracted by this procedure.

Apparatus

A wide mouthed bottle or any other container which can be well stoppered can be used for maceration process. A closed container is essential to prevent the evaporation of menstruum which is mostly concentrated alcohol. Otherwise this may lead to variation in strength as no adjustment in volume is made.
Method
Water or alcohol is used as menstruum and the drug menstruum ratio is 1 : 10.
·       The drug is placed with the whole of the menstruum in a closed vessel for seven days. During this period shaking is done occasionally.
·       After 7 days the liquid is strained and marc is pressed.
·       The expressed liquid is mixed with strained liquid.
·       It is then filtered to make a clear liquid.
·       The final volume is not adjusted.
Explanation
1.     Shaking of the drug during maceration is essential in order to replace the saturated layers around the drug with fresh menstruum.
2.     After straining, the marc is pressed in a filter press, hydraulic press or hand press etc. The marc can be squeezed out of a fine muslin piece, when the quantity of the drug is very small.
3.     The pressed liquid is mixed with the strained liquid and then filtered. No final adjustment is made, since the volume of pressed liquid is likely to vary with the process of pressing the marc. If the final adjustment in volume is made, it will give variation in the concentration of active principle although the volume of the final preparation may be the same.
4.     Filtration is necessary to remove insoluble cell contents obtained during the pressing of marc.
Examples: The tinctures made by simple maceration process are-
1.     Tincture of Orange
2.     Tincture of Lemon
3.     Tincture of Squill
MACERATION WITH ADJUSTMENT
The process is used for unorganized drugs.
Apparatus: Same as simple maceration.
Method:
·       In this process the unorganized drug is placed with 4/5 th of the menstruum in a closed vessel for a period of 2-7 days. During this period, shaking is done occasionally .
·       After the stated period, the liquid is filtered and the volume is made up by passing the remaining 1 / 5 the of the menstruum through the filter.
·       The marc is not pressed.
Explanation
1.     The period of maceration is reduced from 7 to 2 days in some cases, because the unorganized drugs behave like simple chemicals that dissolve in the solvent very easily and quickly.
2.     4/5th of the menstruum is used to keep the drug in contact with it in order to take into account the increase in volume after dissolving the soluble matter of the drug. The volume is made up at the end with 1/5th of the menstruum remained.
3.     The marc left is a compact gummy matter. It does not retain the menstruum and hence it is not necessary to press the marc.
4.     The final volume is made up because all the active constituents of drug get dissolved in the menstruum. Marc is not pressed. hence, there is no change in the concentration of the preparation in case the final volume is made up.
Example
1.     Tincture of tolu
2.     Compound tincture of benzoin.

MULTIPLE MACERATION
Multiple maceration process is carried out in the same way as simple maceration process, but the menstruum used is divided into two parts in double maceration process and three parts in triple maceration process
Double maceration process:
In this process, the drug is macerated twice by using the menstruum which is divided into two parts in such a manner that the same volume is used for each maceration. The quantity of menstruum required for two macerations are calculated as follows:
Volume of menstruum required for first maceration
            Total vol. of menstruum  - Vol. to be retained by the drug       
=                                                                                                  +      Vol. to be retained
                                                     2
Volume of menstruum required for second maceration
=          Total vol. of menstruum - Vol. of menstruum used in first maceration
The volume of menstruum to be retained by the drug is determined by experiment, in a test batch of drug by adding a known volume of menstruum to known weight of the drug. After maceration, straining and pressing of the marc, measured volume volume of liquid is obtained. Difference in the volume and the volume used represents the volume retained by the weighable quantity of the drug used.
·       In double maceration process, the whole of the drug is macerated for 48 hours with the quantity of the menstruum required for first maceration.
·       The liquid is strained and the marc is pressed.
·       The marc is macerated again for 24 hours with the remaining menstruum required for second maceration.
·       The liquid is strained and and the marc is pressed.
·       First and the second liquid is mixed and allowed to stand for 14 days and then filter.
Examples:
The following concentrated infusions are prepared by double maceration process:
1.     Concentrated infusion of orange.
2.     Concentrated compound infusion of chirata.
3.     Concentrated compound infusion of gentian.
Triple maceration process
In this maceration process, the drug is macerated thrice by using the menstruum which is divided into three parts in such a manner that the same volume for three parts in such a manner that  the same volume is used for each maceratin.The quantity of menstruum required for three macerations is calculateas follows:
Volume of menstruum required for first maceration
            Total vol. of menstruum  - Vol. to be retained by the drug        Vol. to be
=                                                                                                  +      retained  by the
                                                     3                                                     drug
Volume of menstruum required for 2nd and 3rd maceration
            Total vol. of menstruum - Vol. of menstruum used in first maceration
=
                                                2
·       The whole of the drug is macerated for one hour with part of menstruum required for first maceration and strained.
·       The marc is macerated again for one hour with the part of the menstruum required for 2nd maceration and strained.
·       The marc is macerated again for one hour with the part of the menstruum required for 3rd maceration and strained.
·       The marc is pressed lightly.
·       The liquid obtained from 2nd and 3rd maceration is pooled and evaporated to a specified concentration. This concentrated liquid is mixed with the liquid obtained from the 1st maceration.
·       90 % alcohol equal to 1/4th of the volume of the finished product is added.
·       Volume adjusted with water and allowed to stand for 14 days and then filtered.
Examples
The following concentrated infusions are prepared by triple maceration process:
1.     Concentrated Infusion of Quassia
2.     Liquid Extract of Senna

PERCOLATION PROCESS
1. Simple percolation process
2. Percolation process for concentrated preparations
            (a) Reserved percolation
            (b) Modified percolation
3. Continuous hot percolation / Soxhlet Extraction / Soxhlation

SIMPLE PERCOLATION
Apparatus:
Three types of apparatus are generally used,
i)      Conical percolator
ii)    Cylindrical percolator
iii)  Steam jacketed percolator [for higher temperature extraction]


Stages:
1.         Size reduction:
The drug to be extracted is subjected to suitable degree of size reduction, usually from coarse powder to fine powder, to
i)      increase the surface area of the drug exposed to the menstruum,
ii)    for uniform packing of the percolator,
iii)  to slow down the movement of the menstruum and
iv)   to ensure complete exhaustion of the drug.

2.         Imbibition:
During imbibition the powdered drug is moistened with a suitable amount of menstruum and allowed to stand for four hours in a well closed container. During this period the drug swells up as the menstruum penetrates the cell walls. The preliminary moistening of the drug is necessary because:
i)      the dried tissue swells when it comes in contact with the menstruum but if packed in the dry condition subsequent swelling will reduce the porosity of the material and choke the percolator,
ii)    the air present in the interstices is removed by menstruum, which will otherwise disturb the packing of the percolator due to which the menstruum will run through the channels results in inefficient extraction,
iii)  it does not allow the fine particles to be washed out of the percolator during percolation.
3.         Packing:
After imbibition the moistened drug is evenly packed into the percolator. Cotton wool or fibres of flax; previously moistened with menstruum is placed on the perforated plate of the percolator.
The packing should not be too tight, it will lead to slow extraction rate. Similarly, loose packing will allow the menstruum to pass through quickly resulting in incomplete contact with the drug.
The drug should occupy 2/3rd capacity of the percolator. After packing , a piece of filter paper is placed over top of the bed, on which small quantity of washed sand is placed to prevent disturbance of the packed material.
4.         Maceration:
After packing sufficient menstruum is added to saturate the material. When the liquid begins to drip from the bottom of the percolator, the tap fitted at its bottom is closed. More menstruum is added if required, so that a shallow layer of menstruum is maintained over the drug bed.
The percolator is allowed to stand for 24 hours to macerate the drug.
5.         Percolation:
After 24 hours maceration, the lower tap is opened and liquid collected therein is allowed to drip slowly at a controlled rate until 3/4th volume of the finished product is obtained.
Sufficient amount of menstruum is simultaneously added over the drug because at no time packed material should be allowed to become dry. After collecting 3/4 th volume, the percolate is tested for complete exhaustion of the drug by various tests.
Tests to check complete exhaustion of the drug:
i)      Take a few ml of the last percolate and evaporate to dryness, it no residue remains - it shows that the drug is completely exhausted.
ii)    The specific gravity of last few ml of percolate is measured. If it is equal to the specific gravity of the fresh menstruum the exhaustion is taken to be complete.
iii)  Specific chemical tests may be performed on the percolate for the drugs containing alkaloids, glycosides, tannins, resins or bitter constituents.
·       The marc  is then pressed and the expressed liquid is added to the already collected percolate.
·       More menstruum is added to produce the required volume.
·       The liquid is then allowed to stand to settle the suspended particles, decanted or clarified by filtration.
Examples:
i)      Tincture of belladonna
ii)    Compound tincture of cardamom
iii)  Strong tincture of ginger etc.

2.(a) RESERVE PERCOLATION
·       In this process, the first portion (about 3/4 th of the final product) of the percolate which contains the maximum amount of active constituents is reserved. Subsequently, percolation is completed as usual until the drug is exhausted but the last part (about 1/4th of the final product) is collected separately.
·       The second dilute part is then evaporated to get a syrupy consistency which is then mixed with the reserved first portion of the percolate.
·       Finally volume is adjusted by adding more menstruum.
Example:
Liquid extract of liquorice
Advantages:
i)      The reserved part of the percolate which contains the maximum amount of dissolved active principles is not subjected to heat, only the dilute portion is evaporated. Hence, the major portion of the active constituents of the drug are saved from deterioration.
ii)    The process is economical as the whole of the percolate is not evaporated.

2.(b) MODIFIED PERCOLATION
In percolation process for preparation of tinctures the drug/percolate (d/p) ratio is about 1:4. The d/p ratio is reduced to 1:3 by modifying the percolation process and hence, there is a lot of saving in heat, time and menstruum.
Percolation is a displacement process. The strong solution of active constituents of drug formed during maceration is displaced by the fresh menstruum when percolation process is started. It is proved that stationary menstruum (menstruum remaining in contact with the drug) dissolves more menstruum is required to exhaust the drug when simple percolation is used. But if continuous percolation stage has suitable breaks by short maceration stages, the d/p ratio can be reduced to 1:3.
Example:
In simple percolation process:
Drug                Imbibition                   Maceration                 Percolation and collect the
(1000 g)          (for 4 hrs)                   (for 24 hrs)                 percolate, i.e. 3/4 the of the
                                                                                                volume of finished preparation
                        Drug : Percolate  =  1000 g  :  4000 ml = 1  :  4
In modified percolation process:
Drug                Imbibition                   Maceration                 Percolation and collect
(1000 g)          (for 4 hrs)                   (for 24 hrs)                 1000 ml of percolate
                                                            Maceration                 Percolation & collect
                                                            (for 12 hrs)                 1000 ml of percolate
                                                            Maceration                 Percolation & collect
                                                            (for 12 hrs)                 1000 ml of percolate
                        Drug : Percolate  =  1000 g  :  3000 ml = 1  :  3

CONTINUOUS HOT PERCOLATION PROCESS / SOXHLET EXTRACTION / SOXHLATION
This process is used for those drugs
·       where the penetration of the menstruum into the cellular tissues is very slow and
·       the solute is not readily soluble into the solvent and
·       the quantity of the menstruum is very less.
In such cases Soxhlet extractor is used where small volume of hot menstruum is passed over the drug time and again to dissolve out the active constituents until the drug is exhausted. The process is known as Soxhlation.


Apparatus:
i)      A flask in which the menstruum is boiled,
ii)    an extraction chamber in which drug is filled, is fitted with side tube and a siphon.
iii)  a condenser.

The drug to be extracted , in suitably comminuted form is usually packed in a ‘thimble’ made of filter paper which is then placed into the wider part of the extractor.
N.B. thimble is used to prevent choking of the lower part of the extractor.
Menstruum is placed in the flask and boiled. The vapor rises through the side tube to the condenser, where the vapor is condensed and fall on the packed drug, through which it percolates and extract out the active constituents.
As the volume of menstruum in the extractor increases, the level of liquid in the siphon also increases till it reaches the maximum point from where it is siphoned out into the flask.
On further heating the menstruum vaporizes while the dissolved active constituents remain behind in the flask. The alternate filling and emptying of the body of the extractor goes on continuously till the drug is exhausted. Thus the same quantity of menstruum is made to percolate repeatedly, about 14 to 15 times through the drug and the active constituents are collected in the flask.
Limitations of continuous hot percolation process:
1.     Physical character of the drug: If the physical character of the drug is such that it would block the soxhlet apparatus then this method is not suitable. e.g opium, gum, resin, orange peel etc.
2.     Solvent: Only pure solvents or constant boiling mixtures (like alcohol-water)can be used for this purpose.
3.     Chemical constituents of the drug: The process is unsuitable for thermolabile active constituents, e.g. enzymes, alkaloids, anthraquinone derivatives, esters etc.


Examples:
 Soxhlation process of extraction is used to
i)      extract cantharidins from cantharides with benzene
ii)    alkaloids from the seeds.

INFUSION
This method is used for those drugs
i)      which are soft in nature so that water may penetrate easily to the tissues and
ii)    the active constituents are water soluble.
Apparatus:
Coffee-pot or tea-pot is the simplest form of apparatus used for preparing infusion. Sometimes special pots known as infusion pots are used for the preparation of infusions. It consists of a loose perforated shelf resting on a projection near the top of the pot.
Method:
In coffee-pot or tea-pot:
i)      The drug is placed at the bottom of the pot. Water is added and it is well stirred three or four times during the period of infusion.
ii)    Infusion can also be prepared by enclosing the drug in a muslin bag and then suspending it just below the level of water in a beaker. Stirring is not required in this case because the water slowly circulates due to the increase in specific gravity of water near the drug.
In infusion pot:
The drug is placed on the perforated shelf. The pot is filled with water and the perforated shelf is adjusted below the surface of water.
*          Final volume is not adjusted.
There are two types of infusions:
1. Fresh infusion,                    2. Concentrated infusion
Fresh infusions:
A fresh infusion is an aqueous solution of active constituents of a vegetable drug prepared by the process of infusion e.g. Fresh infusion of Quassia.
Coarse powder of drug is used in the preparation of infusion. Water is used as menstruum.
Pharmacopoeia states that fresh infusion should be used within 12 hours after its preparation because it gets spoiled due to fungal or bacterial growth.
Concentrated infusions
Concentrated infusions differ from fresh infusions in that the concentrated infusions are prepared by maceration or percolation process and alcohol is used either as a menstruum or as a preservative.
An infusion containing 20 - 25 % alcohol can be stored for sufficiently long time.
e.g. Concentrated compound infusion of chirata and
      Concentrated compound infusion of gentian.



DECOCTION
Decoction is the process in which the water soluble and heat stable constituents of hard and woody crude drugs are extracted out.
Water is used as menstruum and the drug, cut in small pieces, is boiled with the menstruum for 10 to 15 minutes.
After boiling, the liquid is cooled and filtered, more water is passed through the marc to produce the required volume.
Adjustment to final volume is necessary to get a uniform product.
A freshly prepared decoction should only be dispensed and the same must be consumed within 24 hours.
At present no decoction is official in IP or BP.

DIGESTION
This process is a modified form of maceration where the drug is extracted by heating at a particular pressure. This will increase the penetration power of the menstruum, so that there is complete extraction of the drug.
Apparatus:
The apparatus is known as ‘Digestor’ is a vessel made up of metal. The whole of the drug is placed in the body of the digestor; placed the cover over it and bolted it with the help of nuts.
The drug is treated with menstruum for a definite period under specified condition of temperature and pressure.

FACTORS AFFECTING SELECTION OF AN EXTRACTION PROCESS
1.  Nature of the drug
The selection of an extraction process mainly depends on the physical nature of the drug.
Physical nature of the drug
Extraction procedure
·       Hard and woody
·       Soft drugs
·       Unorganised drug
·       By percolation
·       By maceration
·       By maceration and not by percolation because it may block the percolator.

2. Cost of the drug
Costly drugs are extracted by percolation whereas cheaper drugs may be extracted by maceration. Cost involve in size reduction (i.e. comminuting) of the drug should also be taken into consideration.
3.  Stability of drugs
Continuous hot extraction process should not be used for those drugs containing thermolabile active constituents.
4.  Therapeutic value of the drug
The drug containing flavoring agents or bitters etc. which does not have much therapeutic value may be extracted by maceration; but if the drug has considerable therapeutic value then percolation process should be used.
5.  Nature of solvent
If the solvent is water maceration is generally adopted but, if the solvent is volatile then percolation process should be used.
6.  Concentration of the product
Dilute preparations such as, tinctures may be prepared by maceration or by percolation but, concentrated preparations such as, liquid extracts or dry extracts should be prepared by percolation or reserved percolation process.

EXTRACTION METHODS
EXAMPLES
A. MACERATION
i)   Simple maceration



ii)  Maceration  of unorganized drug / Maceration with adjustment

iii)  Multiple Maceration
       a)  Double maceration



       b)  Triple maceration

B. PERCOLATION
i) Simple percolation


ii)  Reserved percolation
iii)  Continuous hot percolation / Soxhlation
C. INFUSION
i) Fresh infusion
ii) Concentrated infusion

D. DECOCTION

i)      Tincture of Orange
ii)    Tincture of Lemon
iii)  Tincture of Squill.

i)      Tincture of Tolu Balsam
ii)    Compound Tincture of Benzoin


i)      Concentrated infusion of orange.
ii)    Concentrated infusion of chirata
iii)  Concentrated infusion of gentian

i)      Concentrated infusion of Quassia
ii)    Concentrated infusion of Senna

i)      Tincture of Belladonna
ii)    Compound tincture of cardamom
iii)  Strong tincture of ginger etc.
Liquid extract of Liquorice
i)      Cantharidin from cantharides
ii)    Alkaloids from seeds

Fresh infusion of Quassia
i)      Concentrated compound infusion of chirata
ii)    Concentrated compound infusion of gentian
No official preparations in IP or BP.


DIFFERENCE BETWEEN MACERATION AND DECOCTION
Maceration
Decoction
1.     Menstruum may be water or hydroalcoholic solvents.
2.     The crude drug is macerated for 3-7 days.
3.     The drug is kept in contact with cold or warm menstruum.
4.     After extraction the marc is expressed.

5.     Extra menstruum is not added to make up the required volume.
6.     Alcohol acts as a preservative, hence it may be dispensed after 24 hours also.
1.     Menstruum is water.

2.     Just 10 to 15 minutes is required to complete the process.
3.     Boiling water is passed through the crude drug.
4.     After extraction the marc is not expressed.
5.     Extra menstruum is passed through the extracted drug to make up the volume.
6.     A freshly prepared decoction should be taken within 24 hours because microorganisms may grow in aqueous medium.
Short note: EXTRACT
Extracts are concentrated preparations containing the active principles of vegetable or animal drugs. The drugs are extracted with suitable solvents and the product is concentrated to one of the three types of extract -
Liquid extract - of which 1 ml usually contains the active constituents from 1 g of the drug.
Dry extract - obtained by completely removing the solvent under reduced pressure.
Soft extract _ obtained by evaporation to a plastic mass.


Short note on EXPRESSION
The resudue of the drug after extraction (often known as the marc) is saturated with solvent. To recover the residual liquid pressure may be applied by a hydraulic press.
The marc is wrapped in cloth, is placed in the perforated inner vessel, which is enclosed in another vessel having an outlet for the expressed liquid. Application of hydraulic pressure to the ram presses the marc against the fixed head, expelling residual liquid.


Comparison between extraction method:
Extraction method
Time for extraction
Temperature
Characteristics of the active constituents
Maceration


Percolation


Digestion

Infusion

Decoction
3-7 days


24 hours


Few days

Short period

15 mins
Room temp


Room temp


Moderately high
Cold or boiling water
Boiling water

·       Soluble in the menstruum
·       Heat stable / unstable

·       Soluble in the menstruum
·       Heat stable / unstable

·       Heat stable

·       Readily soluble

·       Water soluble
·       Heat stable

THEORY OF EXTRACTION OF DRUGS
Mass transfer
Consider a crystal of soluble material (e.g sugarcube) is immersedin asolvent in which it is dissolving. The crystal will be surrounded by a stationary boundary layer of the solvent, with the bulk of the fluid able to move.
The transport of molecules will take place in two stages:
1.     The molecules will move through the boundary layer by molecular diffusion, with no mechanical mixing or movement.
2.     Once material has passed through the boundary layer, mass transfer takes place by bulk movement of the solution, known as eddy diffusion.
Since there is no limit to the vigor of the movement of the bulk of the fluid, so the rate controlling step is the molecular diffusion.
Mass transfer by molecular diffusion can be represented by an equation, similar to conduction of heat transfer, in which
            m                     DA(C1 -C2)  
                        =
            t                                h
where  m = mass transferred in time t
            D = diffusion coefficient of the solute
            A = area of the solute exposed to the solvent
            C1 = concentration of the solute at solid / liquid interface
            C2 = conentration of solute in the bulk phase
            h = thickness of the stagnant layer
Theory of extraction of drugs
Examination of the extraction processes will show that all have certain stages in common:
(i)    Suitable size reduction of the drug
(ii)  Penetration of the drug by the solvent
(iii)Solution of the soluble material within the cells.
(iv)Escape of the soluble material through the cell walls and through the solvent boundary layer surrounding the particles of the drug.
(v)  Separation of the solution and the exhausted drug.
(I) Suitable size reduction of the drug:
From the mass transfer equation it is evident that m/t is proportional to A. If the area (A) is increased then rate of dissolution also increases. So if the size of the drug (plant or animal parts containing the active constituents) is reduced surface area will increase, the consequence of which is the increase of the dissolution rate (m/t) of the active constituent. The ideal size reduction  would be at cellular level but it poses the following disadvantages:
(i)    It is difficult to reduce the size of a drug to its cellular dimension. It requires costly instruments which may not be cost effective.
(ii)  Obviously it will take more time to reduce the size to such a level. Thus prolonged comminution (size reduction) will produce heat that may damage the heat labile constituents of the drug.
(iii)After extraction of such small particles they will make a suspension which will be difficult to filter.
(iv)While reducing the size to cellular level it is most probable that the cell walls will be broken and breakage of cell walls will release unwanted cellular materials like gums, starch, proteins etc. which may produce the filtrate cloudy by the release of  colloidal material.
So the degree of size reduction to be used will depend, therefore, on the botanical structure of the drug.
Name of the drug
Type of the drug
Degree of size reduction
Gentian
Cascara, Belladonna

Ipecacuanha
Soft
Moderately hard

Hard and woody
Sliced and bruised
Coarse and moderately coarse powders
Moderately fine powder
(II) Penetration of the solvent into the drug:
Before drying the fresh drugs are surrounde by a thin film of water. After drying that water film evaporates and becomes porous due to shrinkage. The pores are then occupied by air. To penetrate the cell wall the solvent must have to displace the air first.
When the dry drug  is moistened, the liquid film is again renerated and then the cells imbibe the solvent and swell.
Sometimes to facilitate the removal of air from the pores the solvent and the drug is first taken in a vessel, vacuum is applied - thus air is removed from the pores. Then, when the vacuum is released, pressure of the atmosphere forces the solvent into the drug and penetration is facilated considerably.
(III) Solution of constituents:
Once the solvent has penetrated into the cells solution of the constituents takes place and is governed by the solubility of the constituents in the solvent and again solubility depends on the temperature. So if the temperature is increased the solubility will also enhance.
(IV) Escape of the solution from the cells:
The solute molecules are transferred through the boundary layer or stagnant layer. Factors controlling mass transfer will show that the rate of extraction can be affected in the following ways:
(i)    m / t  ¥  1 / h        i.e. if the thickness of the boundary layer can be reduced rate will ne increased. h can be reduced by agitating the mixture occassionally which disperses local concentrations of the solution, thereby, increasing the concentration gradient.
(ii)  By suspending the drug in a cloth bag or placing it on a perforated plate near to the surface of the liquid the escape of the solution can be hastened. As the constituents dissolve, the density of the solution increases, so that convection currents are established, leading to circulation of the solution followed by the reduction of local concentration surrounding the cloth.
(V) Separation of solution and exhausted drug:
After dissolution the solid materails has to be strained off. Since, the drug absorbs solvent and there is a residue of soluble constituents in that solvent, so the drug is subjected to pressure and sometimes under hydraulic pressure.

PROPERTIES OF SOLVENTS USED FOR EXTRACTING DRUGS
The ideal solvent would be:
1.               It must be cheap.
2.               Non-toxic
3.                It should be stable chemically and physically.
a)               neutral to reaction
b)               not too volatile
c)               non-inflammable
4.               Selective, i.e. it should remove the desired constituents with minimum amount of the inert materials.
N.B.
·       Many extracts are intended for internal use. So the solvents should be selected cautiously.
·       All the above properties of an ideal solvent render the majority of the organic solvents unsuitable.
·       In special cases petroleum ether is required to remove the fat from a drug before extracting  (e.g. some seeds containing fatty coating) the desired active constituents.
Water as a solvent for extraction:
Advantages:
(i)    It is cheap.
(ii)  It has a wide solvent action (e.g. protein, coloring maters, gums, antharaquinone derivatives, most alkaloidal salts, glycosides, sugars and tanins).
(iii)It is non-toxic and can be taken internally.
It is non-inflammable. In industry handling of large volume of volatile solvents may cause accident. Hence the inflammability of a solvent is very important from the point of view of industry.
Disadvantages:
(i)    It is not selective. It dissolves a wide range of substances that  may interfere with the extract’s clarity e.g. gum, protein (coagulated).
(ii)  Water is good medium for mold and bacterial growth. Generally most preparations are preserved with a small amount of glycerine, chloroform or by sterilization.
(iii)Water promotes hydrolysis of many substances and allows enzymatic actions to take place [e.g glycosides such as digitalis].
(iv)Concentration of aqueous solution requires more heat than for most other solvents due to its higher latent heat of evaporation (537 cal / gm).
Ethanol as solvent:
Advantages:
(i)    Reasonably selective, e.g. in a drug containing gum, albuminous matter and a glycoside or an alkaloidal salt, ethanol in a suitable dilution with water would dissolve only the glycoside or the alkaloidal salt, whereas water would usually dissolve all of the constituents.
(ii)  Molds cannot grow in solvent mixture containing more than 20 % ethanol.
(iii)Non-toxic in the quantities prescribed in the medicinal preparations.
(iv)It is neutral, hence compatible with other products .
(v)  Latent heat of vaporization is less than water , so less heat will be consumed to make an extract concentrated.
(vi)Can be mixed in  any combination with water.
Disadvantage:
Cost due increases due to the duty imposed by the Government on it

Questions
Ques. 1 How will you make an infusion of Gentian?            (1991)                         8
Ans:- See the method for Fresh infusion.
Ques. 2. Write the principle, method and equipment used in the following preparations:-(i) Tincture Belladonna   (1992)             4
                        (ii)Tolu Balsam syrup.           (1992)             4
Ans:- Tolu balsam is an unorganized drug. Tolu balsam is taken on a tared vessel and boiling purified water is added to it. The vessel is tightly closed and boiled gently for 30 minutes, stirring frequently. Purified water is added to adjust the specified weight. The preparation is cooled and filtered and then sucrose is added to it. It is heated again in water bath to dissolve the sucrose. Finally sufficient purified water is added to produce the required volume.
Tolu syrup has some aromatic odour and flavour and it is believed to have a mild expectorant action.
Ques. 3. Discuss what do you mean by extraction. How triple percolation is conducted?             (1993)                                                                         4+12
Extraction may be defined as the process in which the animal or plant tissue are treated with specific solvents whereby the medicinally active constituents are dissolved out, cell tissues and most of inactive or inert components remain undissolved. The solvent used for extraction purpose is known as menstruum and residue left after extraction the desired constituents is known as marc.
The various processes used for extraction are: 1. Infusion, 2. Decoction, 3. Maceration, 4. Percolation, 5. Digestion.
The various preparations prepared by using one of the above methods are Infusions, Decoctions, Spirits, Elixirs, Extracts etc. All these preparations are commonly known as ‘Galenicals’.
Triple percolation:- Write Modified Percolation Process.
Ques.4. Describe the percolation process in details with a schematic diagram of a typical percolator.                  (1994, 1996)                                       12
Ans:-  Simple percolation process.
Ques 5 What is reserved percolation?           (1994)                                     4
Ans:- Reserved percolation process.
Ques.6. Short notes on Maceration and Decoction.              (1994)             8
Ans:- Write the difference between Maceration and Decoction.
Ques. 7. Short note on Soxhlet extractor with diagram.       (1994)             8
Ans:- Soxhlet apparatus with diagram.
Ques. 8. Factors affecting the choice of extraction process.            (1994) 8
Ans:- Factors affecting the choice of extraction process.
Ques.9. How does the method of preparation vary for concentrated infusion and infusion.            (1995)
Ans:- See ‘Infusion’.
Ques. 10. Difference between infusion and decoction?        (1995)             2
Ans:- Write yourself.
Ques. 11. What do you by leaching? Name the methods used for the same mentioning their procedure.      (1995)                                                             4+12
Ans:- “Leaching” is same as “Extraction”.
Two main methods of leaching are maceration and percolation. Give the description briefly with diagram.
 


REFERENCE
1.     Introduction to Pharmaceutics - A.K.Gupta [Diploma - 1st year]
2.     Pharmaceutics - R. M. Mehta [Diploma - Ist year]
3.     Remington’s Pharmaceutical Sciences.
4.     Cooper & Guns Dispensing
5.     Cooper & Gun’s Tutorial.
6.     Bentley’s Text Book of Pharmaceutics.