EXTRACTION PROCESSES USED IN PHARMACY

OKPAKO, Eseoghene

What is extraction?�

• Extraction, as the term is used pharmaceutically, 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
• The products so obtained from plants are relatively impure liquids, semisolids or powders intended only for oral or external use.
• These include classes of preparations known as decoctions, infusions, fluid extracts, tinctures, pilular (semisolid) extracts and powdered extracts.

Why do we standardize extraction Procedures?�

• It contributes significantly to the final quality of the herbal drug
• to attain the therapeutically desired portion and to eliminate the inert material by treatment with a selective solvent known as menstruum
• The extract thus obtained may be ready for use as a medicinal agent in the form of tinctures and fluid extracts
• it may be further processed to be incorporated in any dosage form such as tablets or capsules, or it may be fractionated to isolate individual chemical entities such as ajmalicine, hyoscine and vincristine, which are modem drugs.

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Principle of Solid Liquid Extraction

• The principle of solid-liquid extraction is that when a solid material comes in contact with a solvent, the soluble components in the solid material move to the solvent.
• Thus, solvent extraction of plant material results in the mass transfer of soluble active principle (medicinal ingredient) to the solvent, and this takes place in a concentration gradient.
• The rate of mass transfer decreases as the concentration of active principle in the solvent increases, until equilibrium is reached, i.e. the concentrations of active principle in the solid material and the solvent are the same.
• Thereafter, there will no longer be a mass transfer of the active principle from plant material to the solvent.
• Since mass transfer of the active principle also depends on its solubility in the solvent, heating the solvent and use of fresh solvent can enhances the mass transfer.

Factors Affecting Choice of Extraction Process�

1. Character of Drug
2. Therapeutic value of the drug
3. Stability of drug
4. Cost of drug
5. Solvent
6. Concentration of product
7. Recovery of solvent from the marc

Steps involved in the preparation of a plant extract

• Identification
• Authentication
• Collection
• Garbling
• Drying
• Communition
• Extraction
• Filtration
• Concentration
• Drying

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General Extraction Procedures�

• Maceration (Steady state Extraction)
• Infusion
• Digestion
• Decoction
• Percolation (Exhaustive extraction)
• Hot Continuous extraction

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Maceration (Steady state Extraction)�

• the whole or coarsely powdered crude drug is placed in a stoppered container with the solvent and allowed to stand at room temperature for a period of at least 3 days with frequent agitation until the soluble matter has dissolved.
• The mixture then is strained, the marc (the damp solid material) is pressed, and the combined liquids are clarified by filtration or decantation after standing.

Modifications of Maceration

• Repeated maceration may be more efficient than a single maceration, especially where active constituents are more valuable.
• Double maceration is used for concentrated infusions which contain volatile oils.
• Triple maceration is employed where the marc cannot be pressed, the total volume of solvent usually used is large thus the 2^nd and 3^rd macerates are usually mixed and evaporated before adding the 1^st macerate.
• This precludes the use of the process for preparations containing volatile oils.
• In some cases it is desirable to change the physico-chemical properties of the solvent during a single maceration process.

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Infusion�

• Fresh infusions are prepared by macerating the crude drug for a short period of time with cold or boiling water. These are dilute solutions of the readily soluble constituents of crude drugs.
• Infusions now are usually prepared by diluting one volume of concentrated solution to ten volumes of water.
• They are liable to bacterial and fungal growth thus necessary to dispense them within 12hrs of preparation.
• they should be made extemporaneously and in small quantities

Preparation of concentrated Infusions�

• Concentrated infusions are usually prepared by modified maceration or the percolation process, which after dilution resemble the corresponding fresh infusion in aroma and potency.
• The official monographs also recognize certain “concentrated infusions” in which 25% alcohol is added during or subsequent to the infusion process.
• Concentrated infusions are especially prepared in which the active and desirable principles of drug are equally soluble in water or in the menstruum used for both concentrate and infusions.

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Digestion�

• This is a form of maceration in which gentle heat is used during the process of extraction. It is used when moderately elevated temperature is not objectionable. The solvent efficiency of the menstruum is thereby increased.

Decoction

• In this process, the crude drug is boiled in a specified volume of water for a defined time; it is then cooled and strained or filtered.

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Percolation (Exhaustive extraction)�

• There should be uniform moistening of the powdered vegetable drug with menstruum for a period of 4hours in a separate container (imbibition), and then it is packed evenly into a percolator.
• A filter paper is placed on surface followed by a layer `of clean sand so that the top layers of drugs are not disturbed.
• Sufficient menstruum is then poured over the drug slowly and evenly to saturate it keeping the tap at the bottom open to pass off occluded gas.
• Sufficient menstruum is also added to maintain a small layer above the drug and allowed to stand for 24 hours.
• After maceration, the outlet is opened and solvent is percolated at a control rate with continuous addition of fresh volume.
• 75% of the volume of the finished product is collected.
• Marc is pressed and expressed liquid is added to the percolate giving 80% to 90% of the final volume. Volume is adjusted with calculated quantities of fresh menstruum.

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Modifications of Percolation

The reasons for this are thus:

1. If the active substances are thermo-labile, evaporation of large volume of dilute percolate, may result in partial loss of the active constituents.
2. In the case of alcohol- water mixture, evaporation results in preferential vaporization of alcohol leaving behind an almost aqueous concentrate which may not be able to retain the extracted matter in solution and hence get precipitated.

They include:-

• Reserved Percolation
• Cover and Run Down Method

Hot Continuous extraction

• Use of the soxhlet apparatus
• the apparatus consists of a flask, a soxhlet extractor and a reflux condenser.
• The raw material is usually placed in a thimble made of filter paper and inserted into the wide central tube of the extractor.
• Alternatively the drug, after imbibition with the menstruum may be packed into the extractor taking care to see that the bottom outlet for the extract is not blocked.
• Solvent is placed in the flask and brought to its boiling point. Its vapour passes up the larger right hand tube into the upper part of the drug and then to the condenser where it condenses and drops back on to the drug.
• During its percolation, it extracts the soluble constituents.
• When the level of the extracts reaches the top level of syphon tube, the whole of the percolates syphon over into the flask.
• The process is continued until the drug is completely extracted and the extract in the flask is then processed.
• This extraction is series of short maceration

Limitations of hot continuous extraction

• It is not useful when the raw materials contain thermo-labile active constituents because the extraction is carried out at an elevated temperature, and the extract in the flask is also maintained in the hot condition until the process is complete.
• It can be used only with pure solvents or with solvent mixtures forming azeotropes.
• If an ordinary binary mixture is used as the menstruum, the composition of the vapour will be different from the liquid composition.

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Precautions during the extraction process of plants�

• Authentication of plant material should be done before performing extraction. Any foreign matter should be completely eliminated.
• Use the right plant part and, for quality control purposes, record the age of plant and the time, season and place of collection.
• Conditions used for drying the plant material largely depend on the nature of its chemical constituents.
• Grinding methods should be specified and techniques that generate heat should be avoided as much as possible.
• Powdered plant material should be passed through suitable sieves to get the required particles of uniform size.
• Suitable precautions should be taken when dealing with constituents that degrade while being kept in organic solvents, e.g. flavonoids and phenyl propanoids.
• In case of hot extraction, higher than required temperature should be avoided.

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Precautions during the extraction process of plants

• Standardization of time of extraction is important, as: Insufficient time means incomplete extraction.
• The number of extractions required for complete extraction is as important as the duration of each extraction.
• The quality of water or menstruum used should be specified and controlled.
• Concentration and drying procedures should ensure the safety and stability of the active constituents. Drying under reduced pressure (e.g. using a Rotavapor) is widely used. Lyophilization, although expensive, is increasingly employed.
• The design and material of fabrication of the extractor are also to be taken into consideration.
• Analytical parameters of the final extract, such as TLC and HPLC fingerprints, should be documented to monitor the quality of different batches of the extract.

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Extraction Processes for Aromatic Plant Extracts�

The types of volatile isolates that are obtained commercially from aromatic plants are essential oils, concretes, absolutes, pomades and resinoids.

Concrete

This is an extract of fresh flowers, herbs, leaves and the flowering tops of plants obtained by the use of a hydrocarbon solvent such as butane, pentane, hexane and petroleum ether.

Absolutes

Concretes are not widely used in perfumery in their native form but are generally converted into an alcohol-soluble volatile concentrate known as an absolute, i.e. they have to be extracted with alcohol.

Resinoids

Resinoid is an extract of naturally resinous material, made with a hydrocarbon solvent. Resinoids are usually obtained from dry materials.

Pomades

Pomades are obtained by a process known as enfleurage, which is a cold fat extraction method.

Traditional Methods for Extraction of Volatile Oils�A. Hydrodistillation�

• the aromatic plant material is packed in a still and a sufficient quantity of water is added and brought to a boil;
• alternatively, live steam is injected into the plant charge.
• Due to the influence of hot water and steam, the essential oil is freed from the oil glands in the plant tissue.
• The vapor mixture of water and oil is condensed by indirect cooling with water.
• From the condenser, distillate flows into a separator, where oil separates automatically from the distillate water.

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Types of Hydrodistillation

Water distillation

• the material is completely immersed in water, which is boiled by applying heat by direct fire, steam jacket, closed steam jacket, closed steam coil or open steam coil.
• The main characteristic of this process is that there is direct contact between boiling water and plant material.
• During water distillation, all parts of the plant charge must be kept in motion by boiling water; this is possible when the distillation material is charged loosely and remains loose in the boiling water
• Advantages
• It permits processing of finely powdered material or plant parts that, by contact with live steam, would otherwise form lumps through which the steam cannot penetrate.
• are inexpensive,
• easy to construct and suitable for field operation.
• Disadvantages
• Complete extraction is not possible.
• Besides, certain esters are partly hydrolyzed and sensitive substances like aldehydes tend to polymerize.
• Water distillation requires more time, space and more fuel.
• It demands considerable experience and familiarity with the method.
• The process becomes uneconomical.
• Loss of polar compounds
• Oil quality is not reproducible

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Water and steam distillation

• the steam can be generated either in a satellite boiler or within the still, although separated from the plant material.
• water and steam distillation is widely used in rural areas.
• it does not require a great deal more capital expenditure than water distillation.
• the equipment used is generally similar to that used in water distillation, but the plant material is supported above the boiling water on a perforated grid.
• persons performing water distillation eventually progress to water and steam distillation.

Advantages of Water and Steam Distillation over Water Distillation

• Higher oil yield.
• Components of the volatile oil are less susceptible to hydrolysis and polymerization
• If refluxing is controlled, and then the loss of polar compounds is minimized.
• Oil quality produced by steam and water distillation is more reproducible.
• Steam and water distillation is faster than water distillation,
• Many oils are currently produced by steam
• Disadvantages.
• Due to the low pressure of rising steam, oils of high-boiling range require a greater quantity of steam for vaporization - hence longer hours of distillation.
• The plant material becomes wet, which slows down distillation as the steam has to vaporize the water to allow it to condense further up the still.
• To avoid that the lower plant material resting on the grid becomes waterlogged, a baffle is used to prevent the water from boiling too vigorously and coming in direct contact with the plant material.

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Direct steam distillation

• Direct steam distillation is the process of distilling plant material with steam generated outside the still in a satellite steam generator generally referred to as a boiler.
• As in water and steam distillation, the plant material is supported on a perforated grid above the steam inlet.
• Advantages
• A real advantage of satellite steam generation is that the amount of steam can be readily controlled, because steam is generated in a satellite boiler, the plant material is heated no higher than 100° C.
• Consequently, it should not undergo thermal degradation.
• Most widely accepted process for large-scale oil production,superior to the other two processes.
• Disadvantages
• Much higher capital expenditure needed to establish this activity than for the other two processes
• Hydrolytic Maceration Distillation
• Certain plant materials require maceration in warm water before they release their essential oils, as their volatile components are glycosidicallybound. For example bitter almonds (amygdalin), garlic (allicin).

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Expression

• is only used in the production of citrus oils.
• It refers to any physical process in which the essential oil glands in the peel are crushed or broken to release the oil.

Enfleurage

• Certain fl owers (e.g. tuberose and jasmine) continue the physiological activities of developing and giving off perfume even after picking.
• Fat possesses a high power of absorption and, when brought in contact with fragrant flowers, readily absorbs the perfume emitted. This principle, constitutes enfleurage.
• During the entire period of harvest, which lasts for eight to ten weeks, batches of freshly picked flowers are strewn over the surface of a specially prepared fat base (corps), left there for 24 h or more and then replaced by fresh flowers.
• At the end of the harvest, the fat, which is not renewed during the process, is saturated with flower oil.
• Thereafter, the oil is extracted from the fat with alcohol and then isolated.
• After 24 h, the flowers have emitted most of their oil and start to wither, developing an objectionable odor.
• They must then be removed from the corps, which process, despite all efforts to introduce labor-saving devices, is still done by hand.
• Careful removal of the flower (defleurage) is almost more important than charging the corps on the chassis with fresh flowers (enfleurage).

Hot Maceration Process

• In this process, the long enfleurage time is reduced by the immersion of petals in molten fat heated at 45°-60° C for 1 to 2 h, depending upon the plant species.
• After each immersion, the fat is fi ltered and separated from the petals.
• After 10 to 20 immersions, the fat is separated from waste flowers and water.
• Absolute of maceration is then produced from fat containing oil through the process of extraction and concentration under reduced pressure.
• It is mainly used for highly delicate flowers whose physiological activities are lost rapidly after their harvest, such as lily of valley.

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