Pharmaceutical extraction

1. Pharmaceutical
Extraction

2. Objectives
To highlight the purpose of extraction
Demonstrate and highlight the factors that may affect extraction process
Demonstrates of understanding Methods and equipment used for
Extraction, maceration, percolation, digestion, infusion, decoction.

3. History
From earliest times medicines were the product of parts of plants steeped in or
boiled with water. Experience showed that other liquids such as alcohol (e.g.,
wine, brandy, etc.) and vinegar made extraction of ingredients more efficient and
had a preservative action. Prior to extraction processes using these liquids, the
plants had to be prepared and made into the best possible state for ease of
extraction. Plants were cut into small pieces, bruised to soften the woody parts
or dried and then powdered. From the mid-1800s larger scale production was
made possible by industrialisation.

4. Terminology
 Comminution is a general term for various processes used to reduce the size of drug material.
 Slicing was done with the aid of a sharp knife, shears or a root cutter. In the 19th century, machines were developed for large-
scale work.
 Contusion, (or bruising) is the process of reducing a drug to small particles by striking it with several blows. From ancient
times this was normally carried out in a mortar and pestle made of stone, wood, metal or, from the late-1700s of ceramic
composition. An alternative was a simple grater of the type still used in the kitchen for nutmeg or cheese.
 Grinding reduced a substance to a fine powder. This was normally achieved in a mortar and pestle but using a revolving,
shearing action rather than striking.
 Sieving is used to ensure that drugs had been sufficiently ground to produce a suitable particle size. Any oversized particles are
removed from the ground drug.

5. What is extraction?
 Extraction is the method of removing active constituents from a solid or liquid by
means of liquid solvent.
OR
 The separation of medicinally active portions of plant or animal tissues from the
inactive or inert components by using selective solvents.
In this method the wanted components are dissolved by the use of selective solvents
known as menstruum.
 After the extraction unwanted matter is removed.

6. Note
Expression is the physical act of applying pressure to squeeze out oils or
juices from plants. This was normally achieved with a tincture press. This
was normally achieved with a tincture press.

7. Terminologies used in extraction
Marc: The unwanted or insoluble substances left behind after the process of extraction is called marc. These
are not used for further purpose in the process of extraction.
Menstruum: The solvent used in the process of extraction is called solvent. The most commonly used
menstruum is water.
Galenical’s: All preparations that are prepared by using one of the various extraction processes are known as
Galenical’s.
The products obtained from plants are relatively impure liquids, semisolids or powders intended only for oral
or external use. The includes classes of preparation known as decoctions, infusions, fluidextracts, tinctures.
Pilular (semisolid) extracts and powdered extracts. Such preparations have been called galenicals.

8. Steps involved in the extraction of medicinal plants
Size reduction
Extraction
Filtration
Concentration
Drying

9. Purpose of extraction
To obtain the therapeutic portion of dosage form from raw materials and
to eliminate the unwanted or inert material by treatment with solvent
They play a decisive role in the determination of qualitative and
quantitative composition of extracts
The extracts obtained are also utilized for the isolation and
characterization of therapeutically active chemical constituents.

10. Factors affecting extraction
The properties of the extraction solvent
The particle size of the raw materials
The solvent -solid-ration
The extraction temperature
The extraction duration

11. Ideal properties of a menstruum
Highly selective for the compound to be extracted
High capacity of extraction
Should not react with the extracted compound or any other compound in the raw material.
Should have low price and easily available
Should be harmless to man and environment
Completely volatile

12. Factors to be considered in selecting solvents of extraction
Selectivity. The ability of a chosen solvent to extract the active constituent and leave the inert material.
Safety. Ideal solvent of extraction should be nontoxic and nonflammable.
 Cost. It should be as cheap as possible.
 Reactivity. Suitable solvent of extraction should not react with the extract.
 Recovery. The solvent of extraction should be quickly recovered and separated from the extract.

13. Viscosity. Should be of low viscosity to allow ease of penetration.
Boiling temperature. Solvent boiling temperature should be as low as
possible to prevent degradation by heat.

14. Solvents used for extraction
Water
 Alcohol
 Ether
Chloroform
Light petroleum

15. Water (Universal solvent )
It is a polar solvent and is used in the extraction of a wide range of polar compounds
Advantages of Water as solvent
It is very cheap
It is non-toxic
It is inflammable
Highly polar

16. Disadvantages of Water
Wide-solvent actions dissolve a wide range of substances that are undesirable
The growth of molds and bacteria-need of preservatives
Hydrolysis of drug
Required large amount of heat to obtain aqueous concentrate preparation than
non-aqueous
Fermentation may occur-so degradation of the product

17. Alcohol
It is also polar in nature, miscible with water and could extract polar secondary products
Advantages of Alcohol
No mold and bacteria growth if the concentrate is ≥20%
Required small amount of heat to get concentrated preparation
Dissolve selective active constituent of drug
Neutral solvent

18. Disadvantages of alcohol
Costly
Flammable
Volatile

19. Ether
It is a nonpolar solvent and is useful in the extraction of compounds such as
alkaloids, terpenoids, coumarins, and fatty acids.
Advantages
it is miscible with water
has low boiling point
tasteless in nature

20. Disadvantages of ether
Highly volatile
Flammable in nature

21. Chloroform
It is a nonpolar solvent and is useful in the extraction of compounds such as terpenoids,
flavonoids, fats, and oils.
Advantages
 It is colorless
 Sweet smell
 Soluble in alcohol
 Well absorbed and metabolized in the body

22. Disadvantages of Chloroform
It is costly
It has a physiological effect (sedative and carcinogenic effects)

23. Light Petroleum
Advantages of Light Petroleum
It is inflammable
Disadvantages of Light Petroleum
It is costly
It has a physiological effect
It is unsuitable for internal administration

24. Ionic liquid (green solvent)
It is highly polar and extremely heat stable
It is miscible with water and other solvent
Advantages
Excellent solvent that attracts and transmit microwave
It is nonflammable

25. Mechanism of extraction
Plant constituents are usually contained inside the cells.
The solvent used for extraction must diffuse into the cell and swelling of
the cells
Dissolve the desired compounds
Diffusion of the dissolved extractive substances out of the cell

26. Extraction Types

27. Liquid-Liquid Extraction (Solvent extraction)
 In this extraction the components of the liquid mixture are separated by contacting them with a
suitable insoluble solvent which preferentially dissolves one or more components.
 Separation of the components from liquid mixture depends upon the unequal distribution of the
components between two immiscible liquids.
 In this extraction the feed solution is phase 1 and the solvent used for extraction is phase 2.
 Both the feed and solvent forms a homogenous mixture which is separated by contacting them with
one another to separate out one of the two liquids preferentially.
 This type of extraction is most widely used to separate actives and aromatic compounds from plants.

28. Solid phase Extraction
Solid phase extraction is used for isolation, enrichment and purification of
components from aqueous solutions depending upon their physical and chemical
properties.
 It involves contacting of aqueous samples with a solid phase or sorbent, where the
component under consideration is adsorbed on the surface of the solid phase prior to
elution.
This type of extraction is widely used in analytical laboratories.

29. Solid-phase Extraction (Leaching)
Solid-liquid extraction means the removal of constituents from a mixture
of solids by bringing the solid material into contact with a liquid solvent
that dissolves these particular constituents.
Leaching may either be used for production of concentrated solution of a
active principle, or in order to free an insoluble constituents from a
soluble material with which it is contaminated.

30. Methods of extraction
1. Infusion
I. Fresh Infusion
II. Concentrated infusion
2. Decoction
3. Maceration
I. Simple Maceration
II. Modified Maceration
III. Multiple Maceration

31. 4. Percolation
I. Simple percolation
II. Percolation process for concentrated preparation
III. Continuous hot percolation/Soxhlet
5. Digestion

32. 1.Infusion
Drug is placed at bottom of the pot, add water hot or cold (, depending on
whether decomposition of ingredients could occur at higher temperatures ) and
stirred three to four times, stands usually for 15 minutes, After 15 minutes.
Filtering off the liquid without pressing the marc.
Infusions would normally be prepared for immediate use, as there is no
preservative present.
 In some cases concentrated infusions might be prepared by boiling to reduce
the water then adding a preservative such as alcohol.

33. Fresh infusion
Coarse powder of drug plus water (aqueous solution/ menstruum
Used within 12hours after its preparation otherwise infusion get spoilt
due to fungal and bacterial growth
E.g. infusion of orange

34. Concentrated infusion
Prepared by double /triple maceration process
Eight times stronger than fresh infusion
Alcohol (20-25% in concertation) used as solvent
Alcohol can be stored for longer period of time
E.g. concentrated infusion of quassia

35. 2. Decoction
The plant material is boiled for 10-15 minutes in specified volume or boiling water is poured over it
and allowed to stand for thirty minutes.
It is then, cooled and strained or filtered
Suitable for extracting water-soluble and heat-stable constituents
It is used to extract constituents of hard and woody crude drugs
freshly prepared decoction should only be dispensed and the same must be consumed within 24 hours
For example: Cinchona bark, tea , coffee

36. 3. Digestion
This is an extraction method that involves the use of moderate heat (35 -40° C not exceeding 50° C)
 It is used when a moderately raised temperature is needed to increase the efficiency of the menstruum
In this process drug is extracted by heating at a particular pressure to increase the penetration power of the
menstruum, so that there is complete extraction of the drug.
 apparatus used is known as ‘Digestor’ which is a vessel made up of metal.
The whole of the drug is placed in the covered digestor it and bolted with the help of nuts.
The drug is treated with menstruum for a definite period under specified condition of temperature and pressure.
For example extraction of morphine

37. 4. Maceration
In this process solid ingredients are placed in a stoppered container with the whole of
the solvent and allowed to stand for a period of at least 3 days (3 - 7 days) with
frequent agitation, until soluble matter is dissolved.
The mixture is then strained (through sieves / nets), the marc pressed and the
combined liquids clarified (cleaned by filtration) or by decantation, after standing.
This method is convenient and very suitable for thermolabile plant material
Note: Plant material in fine powder form is never used, as it makes subsequent
clarification/filtration of the extract difficult.

38. Process of extraction works by molecular diffusion, which is very slow.
 Occasional shaking assists diffusion and also ensures dispersal of the concentrated
solution accumulating around the surface of the particles, thereby bringing fresh
menstruum to the particle surface for further extraction.
A closed vessel is used to prevent evaporation of the menstruum during the extraction
period and thus avoids batch to batch variation.

39. Types of maceration
I. Simple maceration
II. Modified maceration(maceration with Adjustment)
III. Multiple Maceration

40. I. Simple Maceration / Organized drug
Place crude organized drug in closed vessel and fill with entire volume of menstruum
Shake occasionally for 7 days
Strain liquids, press the marc
Both expressed liquid and trained liquid are mixed and finally preparation if filtered to remove insoluble cell
content and stored. filtrate is not adjusted for volume
Tincture of orange, tincture of capsicum, tincture of lemon
Note: During maceration of organized drugs, the marc is pressed because is considerable proportion of liquid adheres
to it and cannot otherwise be separated. Also, volume is not adjusted because variable amount liquid containing
soluble matter is left in the marc. If the volume is adjusted, a weak product will result

41. II. Modified Maceration/ Unorganized drug
 Drug plus 4/5 of menstruum
 Shake occasionally on day 2 to 7, as specified
 Decant the liquid. Marc is not pressed.
 Filter the liquid and add remaining menstruum (1/5) through the filter to adjust the final volume.
 Example Tincture of tolu, compound tincture of benzoin
Note: In maceration of unorganized drugs, the marc is not pressed because the desirable material is mostly dissolved and the remaining
marc is gummy and slimy. Thus, it is neither practicable nor necessary to press it. In simple terms, Unorganized drug behave like
simple chemical (sugar) and dissolve very easily and quickly (so need not to press the marc)

42. III. 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.
1. Double maceration: Examples Concentrated infusion of orange, Concentrated
compound infusion of chirata, Concentrated compound infusion of gentian .
2. Triple maceration: The maceration process may be carried out with help of heat or
stirring, like Concentrated infusion of Quassia and Concentrated infusion of Senna.

43. 5. Percolation
Percolation is used mostly to prepare tincture and fluid extract. It is also known as
exhaustive extraction.
Types of percolation
I. Simple percolation
II. Percolation process for concentrated preparation
III.Continuous hot percolation/Soxhlet

44. Steps in percolation
 There is generally a percolator (a narrow, conical vessel with a hole at either end)
 The drug to be extracted is subjected to suitable degree of size reduction, usually from coarse powder to fine powder
 The solid ingredients are moistened with the specified amount of menstruum and are filled into the tightly-closed percolator
 All ingredients are then packed and closed with the percolator’s top
 The mass is then covered with additional menstruum to form a shallow layer and macerated in the closed percolator for 24 hours
 A slow drip of liquid is allowed from the percolator’s outlet after it is opened. The percolate is diluted by the addition of additional
menstruum as necessary so that it measures about three-quarters of the finished volume
 Percolate is then prepared by pressing the marc, and then adding the expressed liquid
 The liquid is clarified through filtration or standing and decanting, after adding sufficient amounts of menstruum. This process is
commonly used to extract active ingredients.

45. Three types of percolation
I. Simple percolation process
Examples tincture of belladonna
II. Modified percolation
Repeated maceration is more effective than simple.
Multiple maceration – Solvent divided into equal multiple time considering the solvent
retained by plant tissue.
Used to prepare concentrated preparation.

46. III. Soxhlet extractor (continuous hot extraction)
Used for continuous extraction of component from a solid mixture.

47. What is Soxhlet extraction ?
The original purpose of this apparatus was the extraction of a lipid from a solid
material
Is a procedure for extracting non-volatile and semi-volatile organic compounds
from solids
It can be used if your desired compound has a limited solubility in a solvent,
and the impurity should be insoluble in that solvent
It uses heating, so it cannot be used for substances that degrade due to heat

48. Maceration vs Percolation
Maceration Percolation
Time consuming and also extraction is not
complete
short time and more complete extraction
Not required skilled operator Skilled operator is required
For certain substances which are very less
soluble in solvent and requires only
prolonged contact with solvent.
Special attention should be paid on particle
size of material and throughout process.
•Suitable method for less potent and cheap
drugs
Suitable method for potent and costly drugs

49. Factors to be considered in choosing extraction method
Stability to heat: Heat-stable plant material is extracted using Soxhlet extraction or
microwave-assisted extraction, whereas plant materials that are not heat stable are extracted
using maceration or percolation.
Nature of solvent: If the solvent of extraction is water, maceration is a suitable method but for
volatile solvent percolation and Soxhlet extraction are more appropriate.
Cost of the drug: Cheap drugs are extracted using maceration, whereas costly drugs are
preferably extracted using percolation.

50. Duration of extraction: Maceration is suitable for plant material requiring long exposure to the
menstruum, whereas techniques such as microwave- or ultrasound-assisted extraction are used for a
shorter duration.
Final volume required: large volume products such as tinctures are prepared by maceration, whereas
concentrated products are produced by percolation or Soxhlet extraction.
Intended use: Extracts intended for consumption by human are usually prepared by maceration,
whereas products intended for experimental testing are prepared using other methods in addition to
maceration.

51. Applications of Extraction
It is used in the separation of antibiotics and protein recovery.
It used to recover high-boiling components such as phosphoric acid, boric acid, and sodium hydroxide from
aqueous solutions.
It is used to obtain therapeutically active constituents from plant parts and to eliminate the inert material
It is used to isolate enzymes (renin) and hormones (insulin) from animal sources.
Gelatin is produced by conversion of skin and bone collagen by treatment with lime or diluted acid and is further
extracted with warm water.
It is used in extraction of fixed oils from seeds.

52. References
Soxhlet Extraction https://www.youtube.com/watch?v=LnyTGpm2o5c
 SFE
https://www.youtube.com/watch?v=n2p2zmH3kQ4

53. Questions