Collection of medicinal plants • Drugs may be collected from wild or cultivated plants. • It is known that the active constituents of medicinal plants are affected by many factors and may vary during the course of plant growth. • Proper time of collection is very important to obtain a drug of a good quality. Factors affecting collection 1. Time of the year: The plant may contain a substance in winter that is not present in summer, or its amount varies markedly e.g. Rhubarb contains no anthraquinone in winter, instead it contains anthranols, which in summer, are oxidized to anthraquinones. Colchicum corm is free from bitterness and is devoid of the alkaloid colchicine in autumn, hence is used in Austria as a food, instead of potatoes. Bitterness starts to appear in spring and early summer when it is used as a drug. 2- Time of the day: Some drugs, like Digitalis, contain different amounts of active constituents in different times of the day. Being highest in the afternoon. 3- Stage of maturity and age: • The value and content of active constituents of many drugs depends on the stage of maturity and age. • Conium fruits contain coniin when fruits are mature and unripe. • Santonica flowers are rich in santonin, when unexpanded, when it starts to open, the santonin content decreases. Drying of crude drugs Reasons for drying: 1. To help in their preservation. 2. To fix their constituents, by preventing reactions that may occur in presence of water. 3. To prevent the growth of micro-organisms such as bacteria and fungi. 4. To facilitate their grinding. 5. To reduce their size and weight. Insufficient drying favors spoilage by micro-organisms and makes it possible for enzymatic destruction. Methods of drying Drying is carried out either by natural or artificial methods. 1- Natural drying: this is accomplished by natural air in sun or shade. 2- Artificial drying: this is a rapid method done at well-controlled temperature and is accomplished by: • direct fire. • Use of heated stones. • Use of stoves. • Drying chamber • Drying ovens • Lyophilization (Freeze drying): Frozen material is placed in an evacuated apparatus which has a cold surface maintained at -60 to -80 °C. Water vapour from the frozen material passes rapidly to the cold surface. It is used for drying heat-sensitive substances e.g. antibiotics and proteins. • Chemical drying using desiccators • An absolutely dried drug is that completely freed from water, when exposed to air it absorbs 8-10% of moisture and is called air-dry drug. Stabilization • On long storage, enzymatic reactions will slowly destroy the constituents, because the last traces of water can never be removed. • In order to avoid this degradation, the enzymes should be destroyed before drying, a process usually called stabilization. • The most common method being brief exposure (a few minutes only) of the plant material to ethanol vapor under pressure (0.5 atm). Fermentation • Enzymatic transformation of the original plant constituents is sometimes desirable. e.g. Vanilla pods • The fresh material is placed in thick layers, sometimes covered and often exposed to raised temperatures (30-40 °C) and humidity, so as to accelerate the enzymatic processes. • The fermented product must be dried afterwards to prevent attack by microorganisms, e.g. moulds. Preservation and protection of crude drugs Storage represents the last stage of preparing crude drugs. drugs usually deteriorate along the time of storage, except in few cases e.g. Cascara and Frangula should not be used except after certain period of storage. Certain drugs as Nux vomica are hardly affected by storage. Generally, changes that take place during storage of crude drugs are objectionable, e.g. drugs containing volatile oils gradually lose their aroma. Improper methods of storing and inadequate protection during storage can cause a pronounced deterioration. There are two principal reasons for deterioration: Physiochemical: moisture, heat, air and light. Biological: fungi, bacteria, insects and rodents. Physicochemical factors 1. Moisture: moisture sometimes affects drugs adversely through activating the enzymes (as in cardiac glycosides). 2. Heat: rise of temperature up to 45 activates the enzymes causing decomposition of active constituents. Volatile oil containing drugs are also affected by higher temperatures, their content decreases. 3. Air: oxygen of air oxidizes certain constituents of crude drugs, e.g. linseed and lemon oil, it causes rancidity of fixed oils and resinification of volatile oils. 4. Light: it affects drugs, especially those having marked colours.e.g. yellow colour of Rhubarb changes to reddish tint, white coloured corollas turn brown. Biological factors 1. Bacteria: cotton fibres are rendered brittle by bacterial attack which makes the cotton wool objectionable and dusty. 2. Moulds: the mycelium of delicate hyphae produces an unpleasant mass of clinging particles in powdered drugs. 3. Insects: they seem to attack all drugs but have preferences to certain drugs as ginger, belladonna, kola, liquorice,..... Insects which infest vegetable drugs include beetles, mites and moths. They render drugs porous and powdery. Methods for controlling insects 1. Heat treatment: it is the simplest method and is done by exposing the drug to a temperature of 60-65. it is effective especially for insect eggs which are not affected by insecticides. 2. Fumigation: this is done by volatile insecticidal agents in closed areas e.g. CCL4, CS2, CN. Most fumigants do not kill eggs of insects. It is advisable to repeat fumigation at intervals to obtain better results. 3. Liming: liming of certain drugs as ginger, nutmeg to protect against insect attack provides only partial protection. 4. Low temperature storage: this method is preferred to fumigants and liming. Adult insects, pupae, larvae and eggs are sometimes killed by very low temperatures. 5. Exposure to alternate periods of low and high temperatures: frequently is more effective for killing insects than a prolonged period of low temperature exposure. Rodents: they cause much spoilage of crude drugs during storage, especially if wrapped in paper, cloth or put in cardboard or wooden containers. The presence of rodent's filth, excreta, hairs causes rejection of the drug. Grinding of crude drugs • Regardless of whether the crude drug is to be used for isolation of a pure compound or for manufacture of a simple preparation, the first operation that must be performed is grinding of the plant material to a powder of suitable particle size. • It is important that the particles are of as uniform size as possible. • Excessive dust can clog percolators and result in a turbid extract which is hard to clarify. • • Large particles take a longer time for complete extraction than small ones. Large differences in particle size thus slow down the extraction process. Types of machines used for grinding crude drugs: 1. Hammer mill; a common type for grinding crude drugs. 2. Knife mill; is useful for production of low-dust powders of leaves, barks and roots for subsequent percolation or maceration. 3. Tooth mill; is used for production of very fine powders. Notes: • Grinding produces a certain amount of heat which must be observed when grinding crude drugs containing heat-sensitive compounds. • Mills cooled with liquid nitrogen are available for such purposes. • Cold grinding is also preferable for crude drugs containing volatile oils. • Following grinding, the material must be sifted to ensure the proper particle size. Extracts • Extracts can be defined as preparations of crude drugs which contain all the constituents which are soluble in the solvent used in making the extract. • In dry extracts all solvent has been removed. • Soft extracts and fluid extracts are prepared with mixtures of water and ethanol as solvent. • Tinctures are prepared by extraction of the crude drug with five to ten parts of ethanol of varying concentration, without concentration of the final product. • Plant constituents are usually contained inside the cells. Therefore, The solvent used for extraction must diffuse into the cell to dissolve the desired compounds whereupon the solution must pass the cell wall in the opposite direction and mix with the surrounding liquid. • An equilibrium is established between the solute inside the cells and the solvent surrounding the fragmented plant tissues. The speed with which this equilibrium is established depends on: 1. Temperature 2. pH 3. Particle size 4. The movement of the solvent Choice of solvent • The ideal solvent for a certain pharmacologically active constituent should: 1. Be highly selective for the compound to be extracted. 2. Have a high capacity for extraction in terms of coefficient of saturation of the compound in the medium. 3. Not react with the extracted compound or with other compounds in the plant material. 4. Have a low price. 5. Be harmless to man and to the environment. 6. Be completely volatile. • Aliphatic alcohols with up to three carbon atoms, or mixtures of the alcohols with water, are the solvents with the greatest extractive power for almost all natural substances of low molecular weight like alkaloids, saponins and flavonoids. • According to the pharmacopoeias, ethyl alcohol is the solvent of choice for obtaining classic extracts such as tinctures and fluid, soft and dry extracts. • The ethanol is usually mixed with water: 1- to induce swelling of the plant particles 2- to increase the porosity of the cell walls which facilitates the diffusion of extracted substances from inside the cells to the surrounding solvent. • For extraction of barks, roots, woody parts and seeds the ideal alcohol/water ratio is about 7:3 or 8:2. • For leaves or aerial green parts the ratio 1:1 is usually preferred in order to avoid extraction of chlorophyll. Extraction Procedures There are many procedures for obtaining extracts 1- Infusion 3- Percolation 5- Decoction 2- Maceration 4- Digestion 6- Continuous hot extraction 7- Solvent-solvent precipitation 8- Liquid-liquid extraction 9- Distillation 10- Specific procedures