Chapter 11 Production of crude drugs
The crude drug that reaches the pharmaceutical manufacturing line will have passed through various stages, all of which influence the nature and amount of active constituents present. These aspects will be considered under the headings ‘Source Materials’, ‘Environmental Conditions’, ‘Cultivated and Wild Plants’, ‘Collection’, ‘Drying’, ‘Storage’ and ‘European Regulations’.
It is imperative that correct identification of the source material is made. Adulteration may be accidental, particularly if collection is made from wild plants, or it may be deliberate. Failure in this area can result in poisoning (e.g. hemlock fruits mistaken for other umbelliferous fruits) or inactive products (e.g. substitution of St John’s wort with other vegetable material when demand exceeds supply). For pharmacopoeial drugs, precise macroscopic and microscopic characters are available.
For the isolation of specific constituents, the source can vary, e.g. particular steroids may be obtained from various diverse plants (q.v. Chapter 25) or hyoscine from a number of solanaceous species. Recently a potential problem concerning the production of the oral antiviral against avian flu—Tamiflu® (oseltamivir)—arose from a shortage of Chinese staranise (q.v.), the source of the starting material (shikimic acid, see Fig. 18.8) for the synthesis. However, the toxic Japanese star anise, regarded as an adulterant of the Chinese drug, also contains shikimic acid and could provide an alternative source (D. V. C. Awang and M. Blumenthal, HerbalGram, 2006, 70, 58).
In the article ‘Plant part substitution—a way to conserve endangered medicinal plants’ S. Zschocke et al. (J. Ethnopharm., 2000, 71, 281) explore the possibility of using the leaves of plants that are traditionally used for their barks, bulbs and roots, thus conserving the plant.
Plant growth and development, and often the nature and quantity of secondary metabolites, are affected by temperature, rainfall, aspect, length of day (including the quality of light) and altitude. Such effects have been studied by growing particular plants in different climatic areas and observing variations. The findings of such research are illustrated by work on cannabis by El-Kheir et al. in 1986 in which seeds of cannabis, grown in England and rich in CBD and devoid of THC, when cultivated in Sudan started to produce THC in the first generation and in the second generation contained up to 3.3% THC with a further decrease (down to 0% in some plants) of CBD (see ‘Cannabis’ for explanation of chemistry). However, it is impossible to control all the variables in such experiments, and special laboratories (phytotrons) have been constructed in which all the factors are independently controllable. Even so, a meaningful expression of the results can often present some difficulty. For example, a particular factor may lead to the development of a small plant which, when analysed on a percentage dry weight basis, indicates a high proportion of metabolite, even though the overall yield per plant could be quite low. Conversely, certain nutrients may result in the production of large plants with a somewhat low analytical figure for constituents on a percentage dry weight basis, but yield per plant may exceed that of the control.
Temperature is a major factor controlling the development and metabolism of plants. Although each species has become adapted to its own natural environment, plants are frequently able to exist in a considerable range of temperature. Many tropical and subtropical plants will grow in temperate regions during summer months, but lack frost resistance to withstand the winter. In general, the highest temperatures are experienced near the Equator, but as the temperature falls about 1 °C for every 200 m of elevation, it is possible in, say, Jamaica to have a tropical climate on the coast and a temperate one in the mountains. The annual variations in temperature are just as important as the temperature of the hottest month. At Singapore the annual range of temperature is as little as 1.5 °C, whereas Moscow, with its hot summers and cold winters, has a range of 29.3 °C. In general, the formation of volatile oils appears to be enhanced at higher temperatures, although very hot days may lead to an excess physical loss of oil. The mean optimum temperature for nicotine production in Nicotiana rustica is 20 °C (lower at 11–12 °C and at 30 °C). Several authors have indicated that fixed oils produced at low temperatures contain fatty acids with a higher content of double bonds than those formed at higher temperatures.
The important effects of rainfall on vegetation must be considered in relation to the annual rainfall, its distribution throughout the year, its effect on humidity and its effect coupled with the water-holding properties of the soil. Variable results have been reported for the production of volatile oils under different conditions of rainfall and may in some instances be coupled with the development of glandular hairs. Continuous rain can lead to a loss of water-soluble substances from leaves and roots by leaching; this is known to apply to some plants producing alkaloids, glycosides and even volatile oils. This could account for low yields of some active constituents in wet seasons from plants whose general condition appears to be good.
With Cassia angustifolia (Tinnevelly senna) it has been shown that short-term drought increases the concentration of sennosides A+B but in the longer term causes loss of leaf biomass (H. Ratnayaka et al., Planta Medica, 1998, 64, 438).
Plants vary much in both the amount and intensity of the light which they require. In the wild state the plant will be found where its shade requirements are met, and under cultivation similar shade must be provided. In certain cases research has shown that light is a factor which helps to determine the amount of glycosides or alkaloids produced. With belladonna, stramonium and Cinchona ledgeriana full sunshine gives a higher content of alkaloids than does shade. At Gif-sur-Yvette experiments indicated that with Datura stramonium var. tatula long exposure to intense light brought about a sharp increase in hyoscine content at the time of flowering. An important in vivo reaction in the formation of the antitumour alkaloids of Catharanthus roseus is exemplified by the dimerization of the indole alkaloids catharanthine and vindoline leading to vinblastine; Hirata et al. (Planta Med., 1993, 59, 46) demonstrated that irradiation of intact plants with near ultraviolet light in the range 290–380 nm (peak 370 nm) stimulates the synthesis of dimeric alkaloids, probably by inducing catharanthine oxidation as a trigger reaction. This observation has support from in vitro studies.
It has been shown that under long-day conditions peppermint leaves contain menthone, menthol and traces of menthofuran; plants grown under short-day conditions contain menthofuran as a major component of the volatile oil. Furthermore a long photoperiod for young leaves activates the reduction pathway with conversion of menthone to methol. In studies on the day–night changes in the relative concentrations of volatiles from flowers of Nicotiana sylvestris and other species a marked increase (about tenfold) in aromatic compounds including benzyl alcohol was detected at night, whereas no increase in the volatiles (e.g. linalool, caryophyllene) originating from the mevalonic acid pathway (q.v.) was noted (J. H. Loughrin et al., Phytochem., 1990, 29, 2473).
The daily variation in the proportion of secondary metabolites is probably light-controlled and is discussed more fully under ‘Collection Times’. Many plants initiate flowers only in certain day-lengths, and where flowering is essential this factor must be carefully considered before planting in a new region. Presence or absence of light, together with wavelength range, have a marked effect on the secondary metabolite production of some plants in tissue culture.
The type of radiation which plants receive is also important. With Ocimum basilicum, C. B. Johnson et al. (Phytochemistry, 1999, 51, 507), have found, in relation to herbs raised under glass and receiving no UV-B radiation, that supplementary UV-B radiation increases levels of both the phenyl-propanoids and terpenoids of the leaves. Flavonoids and anthocyanins are also known to be influenced by UV-B radiation. Depletion of the ozone layer and the consequent effect of increased radiation at the earth’s surface has been a topic of much recent speculation. Concerning medicinal plants, R. Karouson et al. (Phytochemistry, 1998, 49, 2273) raised two chemotypes of Mentha spicata which were subjected to increased UV-B radiation equivalent to a 15% ozone depletion over Patras, Greece. In one chemotype essential oil production was stimulated by the treatment while a similar non-significant trend was noted with the other.
The coconut palm needs a maritime climate and the sugar cane is a lowland plant. Conversely, tea, cocoa, coffee, medicinal rhubarb, tragacanth and cinchona require elevation. In the case of Cinchona succirubra the plants grow well at low levels but produce practically no alkaloids. The bitter constituents of Gentiana lutea increase with altitude, whereas the alkaloids of Aconitum napellus and Lobelia inflata and the oil content of thyme and peppermint decrease. Other oil-producing plants may reach a maximum at certain altitudes. Pyrethrum gives the best yields of flower-heads and pyrethrins at high altitudes on, or near, the Equator. It is therefore produced in East Africa and north-west South America. However, vegetative growth is more lush under irrigated conditions at lower altitude, so the propagation farms (for the vegetative multiplication of plants) are, in Ecuador, situated at lower levels than the final commercial farms.
G. A. Statti et al. (Fitoterapia, 2004, 75, 212–216) studied bergamot (Citrus bergamia) grown at different altitudes and solar exposures in Calabria, Italy; they found both chemical (linalool, linalyl acetate composition) and biological (antioxidant and antifungal activities) diversities.
The flowering heads of Arnica montana, grown in Austria in experimental plots at altitudes between 590 and 2250 m showed no altitude effect on the total contents of sesquiterpene lactones and flavonoids but the latter with vicinal-free hydroxy groups in ring B increased with altitude relative to the other flavonoids. Caffeic acid derivatives were 85% higher at the summit compared with the valley (R. Spitaler et al., Phytochemistry, 2006, 67, 407). For a study of the effect of altitude on the podophyllotoxin content of the aerial parts and underground organs of Podophyllum hexandrum populations from the Kumaun region of the Indian Central Himalayas, see M. Nadeem et al., Planta Med., 2007, 73, 388.
Certain drugs are now obtained almost exclusively from cultivated plants. These include cardamoms, Indian hemp, ginger, and peppermint and spearmint for oil production. Others include Ceylon cinnamon, linseed, fennel, cinchona and opium. In other cases both wild and cultivated plants are used. Some plants have been cultivated from time immemorial (e.g. flax, opium poppy and coca). Others are now grown because supplies of the wild plants are insufficient to meet the demand or because, owing to sparse distribution or inaccessibility, collection is difficult. Cultivation is essential in the case of drugs such as Indian hemp and opium, which are subject to government control, and recently for those wild plants in danger of over-exploitation and which have now been given CITES (q.v.) listing. In many cases cultivation is advisable because of the improved quality of the drug which it is possible to produce. The improvement may be due to the following.
For success in cultivation it is necessary to study the conditions under which the plant flourishes in the wild state and reproduce these conditions or improve on them. Small changes in ecology can affect plant products; thus, satisfactory rubber trees grow wild in the Amazon basin but cleared areas converted to rubber plantations have been a failure.
Different plant species vary enormously in their soil and nutritive requirements, and this aspect has received considerable attention with medicinal plants. Three important basic characteristics of soils are their physical, chemical and microbiological properties.
Variations in particle size result in different soils ranging from clay, via sand, to gravel. Particle size is one factor influencing water-holding capacity, and some plants (e.g. Althaea officinalis) which produce mucilage as a water-retaining material contain less mucilage when grown on soil with a high moisture content. Although particular species have their own soil pH tolerances (Datura stramonium 6.0–8.2, Majorana hortensis 5.6–6.4), no marked influence of pH value within the tolerance range has been demonstrated for essential oils (Mentha piperita) and alkaloids (D. stramonium). All plants require calcium for their normal nutrition but plants known as caliphobous plants (e.g. Pinus pinaster and Digitalis purpurea) cannot be grown on chalky soils, probably owing to the alkalinity. In other cases different varieties of the same species may grow on different soils. For example, in Derbyshire, UK, Valeriana officinalis var. sambucifolia is common on the coal measures, but avoids the limestone, where it is replaced by Valeriana officinalis var. mikanii.
The effect of nitrogen-containing nutrients on alkaloid production has received considerable study (solanaceous drugs including Nicotiana, opium); generally nitrogen fertilizers increase the size of the plants and the amounts of alkaloids produced but, as indicated elsewhere, the method of expressing the results of such experiments is important. The effects of nitrogen on glycoside and essential oil contents appear variable; presumably in these cases the final result arises from the general effect of nitrogen on the plant’s metabolism. Nitrogen fertilization has been shown to increase the silymarin content of the fruits of Silybum marianum grown on reclaimed ground. The effect of potassium on alkaloid production shows no consistent trend, but an interesting example is the increase in putrescine production in barley grown on a potassium-deficient medium, where it is possible that the organic base has been formed to act as a substitute for potassium ions. It has long been maintained that trace amounts of manganese are necessary for the successful production of Digitalis purpurea and more recently it was shown that a regimen of manganese and molybdenum feeding over the two years of development of D. grandiflora gives significant increases in glycoside yield.
To ensure success the seeds must be collected when perfectly ripe. If not planted immediately, they should normally be stored in a cool and dry place and must not be kiln-dried. Some seeds such as cinnamon, coca and nutmegs rapidly lose their power of germination if allowed to dry or if stored for quite short periods. Long storage of all seeds usually much decreases the percentage which germinate.
Although seeds are naturally sown at the season when they ripen, it is frequently more convenient, especially in the case of the less hardy exotic species, to defer sowing until the spring. In some cases, however, immediate sowing of the fresh seed is advisable. For example, it has been shown that if the seeds of Colchicum autumnale are air-dried even for a few days, only about 5% germinate in 1 year and some may not germinate for 5 years; whereas if sown as soon as the capsules dehisce, 30% will germinate in the first year. In some instances, as with Datura ferox and foxglove, seeds may remain viable in the ground for many years before germinating. With Erythroxylum coca and E. novogranatense the seeds stored at 4 °C for 24 days gave, respectively, 29% and 0% germination (E. L. Johnson, Planta Med., 1989, 55, 691). Seeds may, if slow germinating, be soaked in water or a 0.2% solution of gibberellic acid for 48 h before sowing; more drastic methods, such as soaking in sulphuric acid in the case of henbane seeds, or partial removal of the testa by means of a file or grindstone, have also been recommended. With Ipomoea purga (jalap) scarification of the seeds has been the secret of success in obtaining 95% germination in eight days (A. Linajes et al., Economic Botany, 1994, 48, 84).
Time of seed-sowing may affect the active constituents, as illustrated by Chamomilla recutita—for 17 cultivars investigated most gave a significantly higher yield of oil if they were spring-sown rather than autumn-sown and the oil composition also varied (O. Gasic et al., J. Ess. Oil Res., 1991, 3, 295, through Chem. Abs., 116, 37955).
The following examples of vegetative propagation may be mentioned.
Plants can be cultivated without soil by the use of an artificial aqueous nutrient medium. The system is suitable for raising plants under laboratory conditions for biogenetic and other studies. It is used commercially for such crops as tomatoes and strawberries but is uneconomic for the large-scale production of common medicinal plants.
S. J. Murch et al. (Planta Med., 2002, 68, 1108) have obtained data showing that a greenhouse hydroponic system can be effectively used for the production of St John’s wort containing the active constituents hypericin, pseudohypericin and hyperforin.
Drugs may be collected from wild or cultivated plants, and the task may be undertaken by casual, unskilled native labour (e.g. ipecacuanha) or by skilled workers in a highly scientific manner (e.g. digitalis, belladonna and cinchona). In the USA the explosive demand for some herbs has led to concern over wholesale uncontrolled collection, so-called wildcrafting, resulting in the over-harvesting of such plants as Panax quinquefolium, Polygala senega, Echinacea spp. and Cimicifuga racemosa (black cohosh). Elsewhere Prunus africana (pygeum bark) found from Nigeria to Madagascar, Rauwolfia serpentina from India, and Turnera diffusa (damiana) from Mexico are other examples of over-exploitation.
A strategy for the sustained harvesting of Camptotheca acuminata (Nyssaceae), the source of the anticancer drug camptothecin, has been described by R. M. Vincent et al., (J. Nat. Prod., 1997, 60, 618). The alkaloid is accumulated in young leaves and by their repeated removal axillary bud outgrowth is stimulated giving an increased harvestable amount of camptothecin in a non-destructive manner. Further studies by S. Li et al. (Planta Med., 2002, 68, 1010) showed that camptothecin accumulates primarily in the glandular trichomes of the leaves and stems with overall variation among Camptotheca species and varieties, and significantly, according to tissue ages and seasons. Details of the two best strains for cultivation are given.
With Hypericum perforatum it has been shown that from the first bud phase to the open flower stage the contents of dianthrones, quercetin derivatives and hyperforin increase; in the unripe fruits dianthrones and quercetin glycosides decrease whereas the hyperforin content increases (D. Tekelová et al., Planta Med., 2000, 66, 778).
The season at which each drug is collected is usually a matter of considerable importance, as the amount, and sometimes the nature, of the active constituents is not constant throughout the year. This applies, for example, to the collection of podophyllum, ephedra, rhubarb, wild cherry and aconite. Rhubarb is reported to contain no anthraquinone derivatives in winter but anthranols which, on the arrival of warmer weather, are converted by oxidation into anthraquinones; also the contents of C-glycosides, O-glycosides and free anthraquinones in the developing shoots and leaves of Rhamnus purshiana fluctuate markedly throughout the year.
The age of the plant is also of considerable importance and governs not only the total quantity of active constituents produced but also the relative proportions of the components of the active mixture. A few examples are given in Table 11.1 but some ontogenetic variation of constituents must exist for all plants.
Table 11.1 Examples of the ontogenetic variation of some metabolites.
| Example | Ontogenetic variation |
|---|---|
| Volatile oils | |
| Mentha piperita | Relatively high proportion of pulegone in young plants: replaced by menthone and menthol as leaves mature |
| M. spicata | Progression from predominance of carvone in young plants to dihydrocarvone in older ones |
| Cloves | Contain about 14–21% of oil; mother ‘blown’ cloves contain very little oil |
| Coriandum sativum | Marked changes in oil composition at the beginning of flowering and fruiting |
| Achillea millefolium | During flowering, monoterpenes (principally 1,8-cineole) predominate in oils from leaves and flowers. Oil obtained during the vegetative period contains principally sesquiterpenes (92%) with germacrane D the major component |
| Laurus nobilis | Highest yield: end of August (Portugal), July (China), Spring (Israel), coinciding with highest level of 1,8-cineole |
| Valeriana officinalis | Highest content in September (valerenic acid and derivatives, and the valepotriates reached maximum in February–March) |
| Cinnamomum camphora | Camphor accumulates in heartwood as tree ages; ready for collection at 40 years |
| Diterpenes | |
| Taxus baccata | Needles contain up to 0.1% 10-deacetylbaccatin which is replaced by large amounts of 2,4-dimethoxyphenol in winter |
| Cannabinoids | |
| Cannabis sativa | Young seedlings contain principally cannabichromene; Δ9-tetrahydrocannabinol is major cannabinoid of adult plants |
| Cardioactive glycosides | |
| Digitalis purpurea | Glycoside content varies with age; purpurea-glycoside A is formed last but eventually reaches a constant maxiumum of 50% of the total glycoside |
| D. lanata | Although highest levels of total glycosides are observed in first-year leaves, those glycosides most important medicinally (e.g. lanatoside C) attain their highest levels in second-year plants |
| Cyanogenetic glycosides | |
| Linum usitatissimum seeds | Monoglucosides (linamarin and lotaustralin) and diglucosides (linustatin and neolinustatin) in developing embryos; diglucosides only accumulate in mature seeds |
| Steroidal sapogenins | |
| Agave sp. | Steroidal sapogenins isolated from young, mature, old and flowering plants had successively fewer hydroxyl groups |
| Yucca sp. | Similar to Agave |
| Dioscorea tokoro | Changes in sapogenin content in first season’s growth |
| Alkaloids | |
| Papaver somniferum | Morphine content of capsule highest 2½–3 weeks after flowering; the secondary alkaloids (codeine, thebaine, narcotine and papaverine) reach their maximum somewhat earlier |
| Datura stramonium | The hyoscine/hyoscyamine ratio falls from about 80% in young seedlings to about 30% in mature fruiting plants |
| Duboisia myoporoides | The hyoscine/hyoscyamine ratio depends both on the developmental stage of the plant and on the position of the leaves on the stem |
| Ipomoea violacea seeds | Lysergic acid amide/chanoclavine ratio increases as the seed matures |
| Steroidal alkaloids | |
| Solanum dulcamara fruits | Solasodine content fluctuates during maturation of fruit; tomatidenol and soladulcidine eventually predominate |
| Citrus glycosides and limonoids | Limonin and naringin levels in grapefruit fall as fruit matures |
| Furanocoumarins | |
| Ammi visnaga | Unripe fruits richest in both khellin and visnagin |
| Tannins | |
| Liquidambar formosana | Seasonable variation of hydrolysable leaf tannis, most rapid changes in the Spring |
| Vanillin | |
| Vanilla planifolia | Highest rate of vanillin biosynthesis occurs 8 months after flower pollination |
There is increasing evidence that the composition of a number of secondary plant metabolites varies appreciably throughout the day and night. In some cases—for example, with digitalis and the tropane alkaloid-containing plants which have been extensively studied—the evidence has been somewhat conflicting in this respect. However, this may be largely due to the methods of analysis employed; thus, throughout the day the overall amount of alkaloid or glycoside may not change to any extent but there may be an interconversion of the various alkaloids or glycosides present. Daily variations of the alkaloids of the poppy, hemlock, lupin, broom, the solanaceous plants and ergot have been reported, also with the steroidal alkaloids of ‘industrial shoots’ of Solanum laciniatum, the cardiac glycosides of Digitalis purpurea and D. lanata, the simple phenolic glycosides of Salix and the volatile oil content of Pinus and Salvia.
Generally speaking, leaves are collected as the flowers are beginning to open, flowers just before they are fully expanded, and underground organs as the aerial parts die down. Leaves, flowers and fruits should not be collected when covered with dew or rain. Any which are discoloured or attacked by insects or slugs should be rejected. Even with hand-picking, it is difficult, certainly expensive, to get leaves, flowers or fruits entirely free from other parts of the plant. In cases such as senna leaf and digitalis the official monographs allow a certain percentage of stalks to be present or a limited amount of ‘foreign matter’ (for definition, see BP/EP and Chapter 16). Similarly, with roots and rhizomes a certain amount of aerial stem is often collected and is permitted in the case of senega root. The harvesting of umbelliferous fruits resembles that of wheat. Reaping machines are used, and the plants, after drying in shocks, are threshed to separate the fruits. Special machines are used to harvest ergot and lavender flowers (illustrations will be found in earlier editions). Barks are usually collected after a period of damp weather, as they then separate most readily from the wood. For the collection of gums, gum resins, etc., dry weather is obviously indicated and care should be taken to exclude vegetable debris as far as possible.
Underground organs must be freed from soil. Shaking the drug before, during and after drying, or brushing it, may be sufficient to separate a sandy soil, but in the case of a clay or other heavy soil washing is necessary. For example, valerian collected from the wild is washed in the streams on the banks of which it usually grows. Before drying, any wormy or diseased rhizomes or roots should be rejected. Those of small size are often replanted. In certain cases the rootlets are cut off; rhubarb, ginger and marshmallow are usually peeled. All large organs, such as calumba root and inula rhizome, should be sliced to facilitate drying. Before gentian root is dried, it is made into heaps and allowed to ferment. Seeds such as nux vomica and cocoa, which are extracted from mucilaginous fruits, are washed free from pulp before drying.
If enzymic action is to be encouraged, slow drying at a moderate temperature is necessary. Examples of this will be found under ‘Orris Rhizome’, ‘Vanilla Pods’, ‘Cocoa Seeds’ and ‘Gentian Root’. If enzymic action is not desired, drying should take place as soon as possible after collection. Drugs containing volatile oils are liable to lose their aroma if not dried or if the oil is not distilled from them immediately, and all moist drugs are liable to develop mould. For these reasons, drying apparatus and stills should be situated as near to the growing plants as possible. This has the further advantage that freightage is much reduced, as many fresh drugs contain a considerable amount (60–90%) of water.
The duration of the drying process varies from a few hours to many weeks, and in the case of open-air drying depends very largely on the weather. In suitable climates open-air drying is used for such drugs as clove, colocynth, cardamom and cinnamon. Even in warm and dry climates arrangements have to be made for getting the drug under the cover of sheds or tarpaulins at night or during wet weather. For drying in sheds the drugs may be suspended in bundles from the roof, threaded on strings, as in the case of Chinese rhubarb, or, more commonly, placed on trays made of sacking or tinned wire-netting. Papers spread on a wooden framework are also used, particularly for fruits from which it is desired to collect the seeds.
Drying by artificial heat is more rapid than open-air drying and is often necessary in tropical countries (e.g. West Africa, where the humidity is very high, and Honduras for drying cardamom fruits). In Europe continuous belt driers are used for large crops such as digitalis. Alternatively heat may be applied by means of open fires (e.g. nutmegs), stoves or hot-water pipes. In all drying sheds there must be a space of at least 15 cm between superimposed trays, and air must circulate freely.
H. N. ElSohly et al. (Planta Medica, 1997, 63, 83) have studied the effect of drying conditions on the taxane content of Taxus needles. When the length of drying extended up to 10 and 15 days as in a shadehouse or in the laboratory the recovery of taxanes was adversely affected. Drying in a tobacco barn, greenhouse or oven, and freeze-drying was generally satisfactory for taxol and cephalomannine recoveries but the recoveries for 10-deacetyltaxol and 10-deacetylbaccatin III were only 75–80% of those expected.
Rapid drying helps flowers and leaves to retain their colour and aromatic drugs their aroma, but the temperature used in each case must be governed by the constituents and the physical nature of the drug. As a general rule, leaves, herbs and flowers may be dried between 20 and 40 °C, and barks and roots between 30 and 65 °C. In the cases of colchicum corm and digitalis leaf it will be noted that the BPC and BP specify the temperatures at which drying is to be done. For rural tropical areas, solar dryers have some distinct advantages over conventional artificial heat dryers and have been introduced into some countries.
Exactly how far drying is to be carried is a matter for practical experience. If leaves and other delicate structures are overdried, they become very brittle and tend to break in transit. Drugs such as aloes and opium may require further drying after importation.
The large-scale storage of drugs is a considerable undertaking. Except in a few cases, such as cascara bark, long storage, although often unavoidable, is not to be recommended. Drugs such as Indian hemp and sarsaparilla deteriorate even when carefully stored. It has been reported that the content of taxol in Taxus baccata leaves and extracts stored at room temperature for one year decreased by 30–40% and 70–80% respectively; storage in a freezer and out of direct sunlight produced no adverse deterioration (B. Das et al., Planta Medica, 1998, 64, 96).
Similarly the alkamides of the popular immunostimulant herb Echinacea purpurea decrease rapidly on storage; N. B. Perry et al. (Planta Medica, 2000, 66, 54) have shown that although drying has little effect on the quantity of alkamides, storage for 64 weeks at 24° produces an 80% loss, and a significant loss even at −18°. Drugs stored in the usual containers—sacks, bales, wooden cases, cardboard boxes and paper bags—reabsorb about 10–12% or more of moisture. They are then termed ‘air-dry’. Plastic sacks will effectively seal the contents. The permissible moisture contents of starch, acacia gum and others will be found in the BP and European Pharmacopoeia. The combined effects of moisture and temperature on humidity and the subsequent water-condensation when the temperature falls, must be considered in drug storage. Drugs such as digitalis and Indian hemp should never be allowed to become air-dry or they lose a considerable part of their activity. They may be kept in sealed containers with a dehydrating agent. For large quantities the bottom of a case may be filled with quicklime and separated from the drug by a perforated grid or sacking. If the lime becomes moist, it should be renewed. Volatile oils should be stored in sealed, well-filled containers in a cool, dark place. Similar remarks apply to fixed oils, particularly cod-liver oil. In the latter case the air in the containers is sometimes replaced by an inert gas. Air-dry drugs are always susceptible to the attack of insects and other pests, so they should be examined frequently during storage and any showing mould or worminess should be rejected.
In order to reduce undesirable microbial contamination and to prevent the development of other living organisms, some plant materials may require sterilization before storage.
To ensure that satisfactory standards for the growing and primary processing of medicinal and aromatic (culinary) herbs are achieved throughout the European Union ‘Guidelines for Good Agricultural Practice of Medicinal and Aromatic Plants’ was issued as a final European version in August 1998. It covers seeds and propagation, cultivation, harvesting, primary processing, packaging, storage and transport, personnel and facilities, documentation, education and quality assurance. Details can be found in ICMAP News, No 6, April 1999 (ICMAP = International Council for Medicinal and Aromatic Plants). Legal requirements covering the manufacture of herbal medicines in Europe have now (2007) been implemented (see Chapter 16: Quality control).