Production and manufacture of Medicinal Plants Lecture (6) Dr Dalia Rasheed

IV- Extraction of Medicinal Plants Definition of Extraction: It is a process that involves the separation of the medicinally active portions of medicinal plants or animal matrix tissues from the inactive or inert components by using selective solvents or gases applying standard extraction procedures. Definition of Drug Extracts (Extractives): These are preparations obtained by treating a certain particle sized herbal drug using a suitable extracting agent to extract their active constituents. Menstruum: the extracting agent of herbal drugs used to extract their active constituents. Miscella: the extract obtained after removal of Menstruum. Marc: the plant residue that was exhausted from the active constituents.

IV- Extraction of Medicinal Plants Drug extracts can be: Directly used as medicinal agent in the form of tinctures or fluid extracts (in liquid dosage forms).

IV- Extraction of Medicinal Plants Drug extracts can be: Further processed (dried) to be incorporated in other dosage forms (e.g. solid dosage forms such as tablets or capsules).

IV- Extraction of Medicinal Plants Drug extracts can be: Fractionated to isolate individual chemical compounds such as ajmalicine (yohimbine), hyoscine and vincristine, which are widely used drugs.

IV- Extraction of Medicinal Plants Types of Herbal Extracts: Aqueous extracts. Fluid or liquid extracts [1:1]. Viscous extracts. Tinctures [1:10]. Dried extracts. Oily extracts. Vinegars.

IV- Extraction of Medicinal Plants Aqueous extracts: (Menstruum is ????) 1.1. Decoctions: These are aqueous extracts prepared by adding cold water to the drug and boiling the mixture for a short period (10 – 20 min.), then cooled and strained or filtered. They are especially useful for preparing hard herbal drugs (such as barks, wood, fruits & roots) with thermostable active constituents. 1.2. Infusions: These are aqueous extracts prepared by adding boiling water to the drug and allow to stand for 10 min., then strained or filtered. They are usually applied for leaves, flower & herbs.

IV- Extraction of Medicinal Plants Aqueous extracts: 1.3. Macerates: These are aqueous extracts prepared by adding cold water to the drug and allow to stand for several hours at room temperature, then strained or filtered. They are suitable for drugs rich in mucilage. Decoction Infusion Macerate

IV- Extraction of Medicinal Plants Fluid or Liquid extracts: These are hydroalcoholic extracts prepared by percolation or maceration. They contain alcohol as solvent or preservative. They are made so that each 1 ml of the extract contains the active constituent of 1 gm of the herbal drug [1:1]. They have bitter taste and should be used after addition of flavoring or sweating agents. They serve as main ingredients in syrup preparations. Viscous extracts: These are semisolid preparations obtained by partial evaporation or "careful concentration” of fluid extracts.

IV- Extraction of Medicinal Plants Fluid or Liquid extracts: Viscous extracts:

IV- Extraction of Medicinal Plants Tinctures: These are alcoholic or hydroalcoholic preparations containing alcohol in amount ranging from 25 - 85 %. The alcoholic content protects against microbial growth and helps keeping the alcoholic soluble extractives in solution form. They are made so that each 10 ml of the extract contain the active constituents of 1 g of the herbal drug [1:10].

IV- Extraction of Medicinal Plants Tinctures: Examples: Tincture Cannabis, Tincture Guaiac gum & Tincture Opium (laudanum).

IV- Extraction of Medicinal Plants Dried extracts: These are solid extracts obtained by concentration and complete drying of liquid extracts. They are used as component in the oral solid dosage form (tablets & capsules).

IV- Extraction of Medicinal Plants Oily extracts: These are oily preparations obtained by macerating the herbal drugs in vegetable oil (almond or olive oils). Examples: Saw Palmetto Fruit Oily Extract (use???) & Arnica oil. Vinegars: These are acidic extracts obtained by extraction of drugs with dilute acetic acid. Examples: Squill vinegar.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Decoction: The crude drug is boiled in a specified volume of water for a defined time (10 – 20 min.); it is then cooled and strained or filtered. It is suitable for extracting water-soluble & heat-stable constituents. The starting ratio of crude drug to water is fixed (1:4 or 1:16); the volume is then brought down to one-fourth its original volume by boiling during the extraction procedure.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Infusion: The crude drug is macerated for a short period of time (10 min.) with boiling water; it is then strained or filtered. Thus, infusions are dilute solutions of the readily soluble constituents of crude drugs. Maceration: The crude drug is placed in a stoppered container with a liquid solvent and allowed to stand at room temperature for a period of at least 3 days with frequent agitation until the soluble matter are completely exhausted. The mixture then is strained, the marc is pressed, and the combined liquids are clarified by filtration or decantation.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Digestion: This is a form of maceration in which gentle heat is used during the process of extraction to increase the solvent efficiency of the menstruum. It is used when moderately elevated temperature is not objectionable. Percolation: The plant material are moistened with an appropriate amount of the specified menstruum and allowed to stand for approximately 4 hours in a well closed container. Then, the mass is packed in the percolator (a narrow, cone-shaped vessel open at both ends) to about three-quarters of the percolator volume.

Percolators

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Percolation: Additional menstruum is added and the mixture is allowed to macerate in the closed percolator for 24 h. The outlet of the percolator then is opened and the liquid contained therein is allowed to drip slowly. The marc is then pressed, the expressed liquid is added to the percolator with additional menstruum and the process is repeated till exhaustion of the plant material. The combined liquid is clarified by filtration or decanting. This procedure used most frequently for preparation of tinctures and fluid extracts.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Ultrasound Extraction (Sonication): It involves subjecting the herbal material soaked in the menstruum to ultrasound waves with frequencies ranging from 20 - 2000 kHz.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Ultrasound Extraction (Sonication): Advantages: sonication increases the permeability of the menstruum into the cell walls and produces cavitation. Disadvantages: its large-scale application is limited due to the higher costs. The occasional but known deleterious effect of ultrasound energy (more than 20 kHz) on the active constituents of medicinal plants through formation of free radicals and consequently undesirable changes in the drug molecules. Applications: Extraction of Rauwolfia root.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Hot Continuous Extraction (Soxhlet): E A (menstruum) D C

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Hot Continuous Extraction (Soxhlet): In this method, the finely ground crude drug is placed in a porous bag or “thimble” made of strong filter paper, which is placed in chamber E of the Soxhlet apparatus. The extracting solvents in flask A is heated, and its vapors condense in condenser D. The condensed extractant drips into the thimble containing the crude drug, and extracts it by contact. When the level of the liquid in chamber E rises to the top of siphon tube C, the liquid contents of chamber E siphon into flask A. This process is continuous and is carried out until a drop of solvent from the siphon tube does not leave residue when evaporated.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Hot Continuous Extraction (Soxhlet): Advantages: large amounts of drug can be extracted with a much smaller quantity of solvent. This effects tremendous economy in terms of time, energy and consequently financial inputs.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Supercritical Fluid Extraction (SFE): What is a supercritical fluid???? Phase diagram for a typical matter at a fixed volume Triple point Critical point

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Supercritical Fluid Extraction (SFE): Supercritical fluid is a state of matter that is intermediate between a gas and liquid in its properties. This state is formed when a gas or liquid solvent is subjected to temperature and pressure condition exceeding a particular point known as the “Critical point”, which is characteristic for every matter. Beyond the critical point, the matter is neither a gas or liquid, but physically, it possess the properties of both phases (Solubility approaching liquid phase, Diffusion approaching gas phase). The solvent strength of a supercritical fluid can be varied by changes in the pressure and to a less extent in the temperature. Supercritical fluids must be cheap, inert, and nontoxic for use.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Supercritical Fluid Extraction (SFE): Many supercritical fluids are gases at ambient condition. CO2 & Argon (Ar) comprise the most commonly used agents in SFE. Advantages of CO2 as SF: favorable physical properties, cheap, safe and abundant. Disadvantages of CO2 as SF: it possesses several polarity limitations. Organic solvents are frequently added to the CO2 extracting fluid to alleviate the polarity limitations (Co-solvency).

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Supercritical Fluid Extraction (SFE):

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Supercritical Fluid Extraction (SFE):

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Supercritical Fluid Extraction (SFE): Advantages: The extraction of constituents is achieved at low temperature, which strictly avoids damage from heat. No use of organic solvents and no solvent residues. Environmentally friendly extraction procedure. SFE is generally fast. The rate of mass transfer between a sample matrix and an extraction fluid is determined by the rate of diffusion of a species in the fluid and the viscosity of the fluid —the greater the diffusion rate and the lower the viscosity, the greater will be the rate of mass transfer. The solvent strength of a SF can be varied by changes in the pressure and the temperature, giving a wider range of polarities.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Supercritical Fluid Extraction (SFE): Applications: extraction of pesticides, environmental samples, foods, fragrances, essential oils, polymers and natural products; such as: Extraction of vitamin E from soybean oil and its purification. Decaffeination of coffee (it was the first process to be commercialized in 1978). Coffee beans should be pre-wetted by soaking in water for about 2 hours for efficient extraction of caffeine from coffee beans by supercritical carbon dioxide.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Phytosols extraction method: Advanced Phytonics Limited (Manchester, UK) has developed a novel patented technology termed “Phytonics process”. This technology uses non-flammable solvents called “Phytosols”, which are non-chlorinated haloalkanes. The most common solvent used is 1,1,2,2-tetrafluoroethane (hydrofluorocarbon-134a) (HFC-134a) with the following characters: A boiling point of −26.3 °C at atmospheric pressure. It is not flammable or toxic. Unlike chlorofluorocarbons (Freon) used as refrigerants, it does not deplete the ozone layer. It is a poor solvent: it does not mix with mineral oils or triglycerides and it does not dissolve plant wastes (advantage or not???).

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Phytosols extraction method: Advantages: No temperature: it is cool and gentle and its products are never damaged by exposure to temperatures. No vacuum stripping: thus no loss of precious volatiles. No acid hydrolysis or oxidation (in absence of oxygen): as it is carried out entirely at neutral pH. Highly selective: offering a choice of operating conditions and hence a choice of end products. Economic: it requires a minimum amount of electrical energy.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Phytosols extraction method : Advantages: Environmentally friendly: it releases no harmful emissions into the atmosphere and the resultant waste products (spent biomass) are innocuous and pose no effluent disposal problems. Safe: the solvents used are not flammable, toxic or ozone depleting and completely recycled within the system.

IV- Extraction of Medicinal Plants General Methods of Extraction of Medicinal Plants: Phytosols extraction method : Applications: Extraction in biotechnology e.g. production of antibiotics. Extraction of high-quality essential oils, oleoresins, natural food colors and flavors. Production of top quality pharmaceutical-grade extracts, pharmacologically active intermediates and phytopharmaceuticals. Refining crude products obtained from other extraction processes. It provides extraction without waxes or other contaminants.