14: Herb Manufacture, Pharmacy, and Dosing

CHAPTER 14 Herb Manufacture, Pharmacy, and Dosing

Barbara J. Fougère, Susan G. Wynn

Aplethora of products is available on the market. Why wouldn’t we simply recommend that our clients go and buy one off the shelf for their animal? Quite apart from the standard practice of prescribing according to individual needs, one of our main concerns is whether the practitioner can be confident of product quality. Is it safe? Will it be effective? Quality control is covered in Chapter 8, and integral to this is the matter of how herbs are manufactured. This chapter looks at how herbs are made into various useful forms and how they can be dispensed and dosed appropriately.

HERB VARIABILITY

It is well established that the same species of herb can vary widely depending on cultivation practices. Differences in water availability, fertilizer type, temperatures, and other factors can make for more or less concentrated herbs. The sophisticated quality control procedures that are needed to monitor these variations are not available to veterinarians but may be used by some companies. The best advice for minimizing the effect of this variability on patients is to find a reputable herbal pharmacy or supplier and to use herbal products consistently.

GOOD MANUFACTURING PRACTICE

To know which herbs a patient is receiving, practitioners must make their own or purchase good-quality herbal medicines and formulate from these. Manufacture of herbal medicinal products should be undertaken according to Good Manufacturing Practice (GMP), with the goal of providing quality assurance and safety in all manufactured products. It is important to know that the chosen manufacturer complies with these standards, which ensure that the right species is being used, that it is being produced and stored properly, and that it is not contaminated or adulterated.

Compared with well-defined synthetic drugs, herbal medicines exhibit some marked differences, namely,

• They are defined biologically rather than chemically

• The active principles are frequently unknown

• Standardization, stability, and quality control are feasible but problematic

• The availability and quality of raw materials are frequently problematic

It is no surprise that manufacture of herbal products under GMP is more complex than that of conventional drugs. However, GMP is not applied to growing, harvesting, drying, or sifting of herbs, nor is it related to preliminary processing of herbal oils. So, the sources of raw material and the good practices of manufacturing processes are certainly essential steps in the quality control of herbal medicines. One critical issue for safety and efficacy is identification of the right plant species. Substitution of one herbal raw material for another can be a serious problem when it is a subspecies, the wrong species (e.g., Aristolochia for Stephania causing renal failure), or a less active plant part, or when an herb is contaminated by another species (e.g., digitalis in comfrey).

Therefore, it is important that material specifications for crude herbs should include information on source, part used, description, and identification, as well as reports on contamination with pesticides, microbes, mould, pests, or foreign matter and on purity or potency. Herbs have been contaminated with heavy metals (e.g., cadmium and arsenic) and have been adulterated with drugs (e.g., nonsteroidal anti-inflammatory drugs). Any contamination could compromise the safety and efficacy of an herbal preparation, even when the practitioner decides to make his or her own herbs in practice; a specification form should be requested when bulk purchases are made.

In the first instance then, the source and quality of raw materials play a pivotal role in the quality and stability of herbal preparations. Other factors such as use of fresh or dried plants, season, light exposure, water availability, nutrients, period and time of collection, storage and transportation of raw material, age and part of the plant collected, and methods of collecting, drying, and packing can greatly affect the quality and consequently the therapeutic value of herbal medicines. These factors also account for variability of individual constituents or markers in herbal preparations. This variability is not a feature of conventional drug manufacture.

STANDARDIZATION

The American Herbal Products Association (AHPA) defines standardization very broadly as “the complete body of information and controls that serves to optimize the batch-to-batch consistency of a botanical product. Standardization is achieved by reducing the inherent variation of natural product composition through quality assurance practices applied to agricultural and manufacturing processes.”

Standardized extracts are common in trade and are prepared by maceration, percolation, or distillation (volatile oils). Ethanol, water, or mixtures of ethanol and water are used for the production of fluid extracts. Solid or powdered extracts are prepared by evaporation of solvents used in the process of extraction of the raw material.

Advances in the processes of purification, isolation, and measuring of certain phytochemicals have made possible the establishment of appropriate strategies for the analysis of quality and the process of standardization of herbs toward maintaining as much as possible the homogeneity of the plant extract. Among others, gas chromatography, high-performance liquid chromatography, thin-layer chromatography, mass spectrometry, infrared spectrometry, and ultraviolet/visible spectrometry, used alone or in combination, can be successfully used for standardization and to control the quality of the raw material and the finished herbal products.

However, plants contain several hundred constituents, and some of them are present at very low concentrations; despite these technologically advanced chemical analytical procedures, rarely do phytochemical investigations succeed in isolating and characterizing all secondary metabolites present within a plant extract. Also, marker substances used in standardization and quality control tests may not really account for the therapeutic action reported for an herbal product.

As well, marker compounds may exhibit wide variation, for example, Echinacea purpurea products in Australian products have demonstrated wide variation in such markers as alkylamides and caffeoyl phenols. Thus, standardization and quality control of raw material and herbal preparations are challenging compared with these processes in standard drug manufacturing, and their relevance to therapeutic value may be questionable. Standardization can enhance only the reproducibility of a preparation—not its quality.

The AHPA white paper on standardization notes that the concept of standardization has been misunderstood to describe the “control or isolation of particular constituents. On the contrary, standardization is a complex, multifaceted process that relies primarily on appropriate controls of raw materials and the manufacturing process. Quantitative testing such as bioassays or measurement of specific constituents may be used in addition to, but never in place of, these other measures, because analytical measurements by themselves can only confirm, not control, “batch-to-batch consistency.”

SOURCES OF HERBS

Commercial herbal preparations draw plant material from two main sources: wildcrafting and cultivation. Wildcrafting involves the harvesting of plants from the wild by trained collectors; these herbs are preferred by many herbalists. Cultivated plants are specifically grown for the trade and are the best sources of endangered or threatened herbs. Herbalists and especially herb pharmacies have voiced concern that plants in cultivation are not of the same quality as wildcrafted herbs. Herb pharmacies are investigating this issue in partnership with academic centers; no clear answers have been revealed as yet.

Wildcrafting has led to the endangerment of a number of herbs, including goldenseal and ginseng. There is concern about others—even wild echinacea in the United States and thyme in Europe. Some herbs have very limited habitats, and although they are not now endangered, they are subject to trends and shifts in popularity. When herbs are bought from a supplier who wildcrafts, the purchaser should make sure that the label says “ethically wildcrafted.” This means that the wildcrafter protects the herbs by harvesting only a small percentage. It is MUCH better for practitioners to find an organic cultivated source for these herbs.

A third source of herbs may be your own garden. Home production of locally endangered plants lightens the strain of commerce in that plant and provides the herbalist with an opportunity to better study his or her medicine from germination to patient administration. Even if regulatory pressures discourage veterinarians from assuming liability for their home-prepared herbal medicines, the use of home-grown plants in their own personal family pharmacy supports the learning process and is highly recommended for recreation and exercise. An excellent reference for home medicine-makers is Cech (2000).

FORMS OF HERBAL MEDICINES

Veterinarians are usually too busy to make their own herbal medicines, but it is important that they know how the herbs are prepared. Herbal products begin as fresh or dried plant, or as plant extracts (Box 14-1). These preparations form the basis for capsules, tablets, pills, salves, oils, liniments, juices, and tinctures.

Which form is commercially available or preferred depends upon whether the main constituents of an herb are lipid or water soluble, as well as on their palatability and level of patient acceptance. Whole fresh or dried plant is obviously the form that keeps all constituents intact, but it is the form that requires greater volume and may result in poor taste and potentially poor bioavailability; however, for ruminants and horses, this form may be the most acceptable.

Dried Forms

Dried herbs

Dried bulk herb has been harvested, dried, and sometimes powdered. Dried powdered herb may be supplied as a dried bulk herb, as loose powder, or in capsules. Gardeners may dry herbs from their own plots with basic knowledge of the plant part used and the correct harvest time. Aerial parts may be cut and bundled together to be hung on a rafter in a dry spot or on drying screens until dehydrated. A gentle air current can speed drying time, which cuts down on microbial contamination. The herb must be protected against excessive heat and light and not left exposed for long after it is dried. Once the herb is completely dried, it can be stripped from the stalks and stored in jars with lids, or in tins. This form can be used for teas or decoctions, or can be fed directly mixed in the animal’s food, which is probably ideal. Dried herbs are best stored under cold conditions (less than 11° C) to limit the hatching of insect eggs, which inevitably infest organic herbs.

US Pharmacopoeia (USP) Definitions

Fluid extract: Alcoholic or hydroalcoholic preparation providing a dry herb : liquid strength ratio of 1 : 1. These very concentrated extracts require vacuum equipment.

Fresh plant fluid extract: Alcoholic or hydroalcoholic tincture prepared using 1 part fresh herb by weight for 1 part liquid by volume. This weight : volume relationship takes into account the water content in fresh plants. (The AHPA adds that fluid extracts are also sometimes 1 : 2 biomass : solvent, and that traditionally dried herb is used.)

Soft extract: An extract that has the consistency of a thin to thick liquid or paste.

Solid extract: A USP fluid extract that has been evaporated or vacuum extracted to 4 parts herb for every 1 part extract.

Powdered extract: A powdered version of a USP solid extract or fluid extract, prepared by evaporation to remove liquid. The concentration can range from 1 : 1 to 10 : 1, or greater.

Standardized extract: A powdered extract prepared by any of the previous methods, with certain constituents (either a particularly active ingredient or a marker compound) standardized to a specific preset level in every batch of extract. These extracts may or may not change the ratio of constituent ingredients within the plant to each other, depending on which compound is chosen and how the plant is standardized.

Galenical extract: A pharmacopoeial extract prepared according to guidelines from various pharmacopoeias, such as the British Pharmaceutical Codex, that dictate the method of preparation, the solvent used (usually alcohol and water), and the ratio of herb material to final extract. In modern times, this extract is often formed into a tablet or capsule.

Dried extracts

The herb has been concentrated by simmering in water (see Infusions and Decoctions, later) removing the residue, and spraying the concentrated “tea” in a vacuum chamber, resulting in powder or granules of remaining concentrated herbal constituents. One caution in the use of this form of herb is that because the solvent used is water, the extract may miss active constituents that are only alcohol soluble. A commonly provided form is a 4 : 1 or 5 : 1 extract, which allows veterinarians to recommend fewer capsules than if powdered herb is used. Dried extracts may also be available as loose powders or granules, encapsulated powders or granules, or pressed tablets.

Tinctures and Liquid/Fluid Extracts

These are the most commonly dispensed liquid forms of herbs; combining liquids makes formulation and prescribing easy. The advantages of tinctures include the following:

• Alcohol based (good solvent and preservative at 25%–100%)

• Concentrated

• Good shelf-life

Alcohol is a useful solvent and forms tinctures with nearly unlimited shelf-life, unless precipitation occurs over time. For extraction of water and lipid-soluble herb components, alcohol and water proportions may range from 20 : 80 to 40 : 60 (vodka is conveniently made this way) up to 100% alcohol. The percentage of alcohol needed varies according to the constituents to be dissolved, and good manufacturers vary the alcohol:water ratio to reflect the ideal extract for each individual herb (Table 14-1). For instance, mucilage does not dissolve well in ethanol, so a low alcohol percentage is best at 15% to 25%, and resinous herbs dissolve only in high-alcohol menstruum (90%+). Many herbs extract well in plain 80 proof (40% alcohol) vodka. Tinctures must contain at least 24% to 26% pure alcohol to be well preserved. Some manufacturers decoct herbs that are traditionally used this way (concentrated through multiple boiling water extractions), then preserve with alcohol.

TABLE 14-1 Solubility of Herb Components

Component	Example Plants	Solubility
Alkaloids	Goldenseal, lobelia, bloodroot, corydalis	High solubility in alcohol, low water solubility. Vinegar may enhance extraction
Essential oils	Peppermint, lavender, thyme, tea tree	High solubility in alcohol, low water and glycerin solubility. Extract well into fixed oils
Glycosides	Hawthorn, licorice, milk thistle, gentian	Soluble in water and alcohol
Mucilage	Slippery elm, marshmallow, purslane	Water soluble only and best extracted in cold water; will precipitate if alcohol is added. Usually used fresh or simply dried
Polysaccharides	Astragalus, mushrooms, boneset, echinacea	Water soluble only, will precipitate if alcohol is added
Resins	Kava, rosemary, grindelia, propolis, sweetgum	Soluble in alcohol and hot oil; not soluble in water. To make an ointment, use tincture in 95%—100% alcohol; add oil, then gently heat to evaporate the alcohol
Saponins	Ginseng, wild yam, yucca	Water soluble
Tannins	Witch hazel, blackberry leaf, self heals	Water and glycerin soluble

One interesting variation on this theme is to extract some of the herb in 100% alcohol and decoct the other portion of herb, then add the two together at an optimal proportion; presumably, this allows maximal extraction of both water- and alcohol-soluble ingredients. It is wise to know what the concoction smells and tastes like when it is first made, so that one can check for spoilage later.

Alcohol extracts are concentrated and are believed by herbalists to have the most rapid gastrointestinal absorption rate and bioavailability of active components. It is likely that alcohol acts to keep these active components in solution after ingestion, thus facilitating their absorption into circulation. Alcohol extracts taste terrible to most dogs and cats, but the small amount required, in addition to the ease with which they can be combined by the herbalist, makes liquid extracts popular.

Making tinctures and fluid extracts

The folk method of preparing tinctures is simply to loosely pack a jar with fresh or dried cut herb, then to pour solvent over it to cover completely. To make a more standardized extract, the weight : volume method is used to describe the concentration of a tincture. The herb is weighed and the volume of the solvent is added in some proportion to the weight (grams of herb to milliliters of solvent, for instance), and typical proportions are 1 : 2 for fresh herb and 1 : 5 for dried herb. For example, 2 ounces by weight of an herb may be placed in a small jar, then covered with 4 oz of vodka, to produce a 40% alcohol 1 : 2 tincture. Strong herbs, such as lobelia and pokeweed, are often tinctured at lower concentrations (1 : 10) to guard against overdoses.

Tinctures are prepared with use of the herb (the “marc”) and a solvent (the “menstruum”). The herb is prepared before it is tinctured. Fresh herb should be minced finely to destroy as many cell walls as possible. Because fresh herbs contain variable amounts of water, they should be tinctured in the higher percentages of alcohol. Fresh roots should be sliced thinly or chopped finely. Some are very tough and require pruning shears for cutting (use of a meat cleaver is effective, but root pieces fly all over the place). Roots are best used fresh in the home pharmacy because when dried, they become too hard to be chopped without commercial equipment. Dried herb aerial parts are simply crushed, ground in a food mill or coffee grinder, or pressed through a screen before tincturing. Dried herbs swell with water when the menstruum is added, so room must be left in the macerating jar to account for this. The herb is usually “moistened” overnight before the menstruum is poured, to minimize any change in volume. If seeds are used, they should be dried for a few hours and separated from any chaff, then ground or bruised before tincturing.

The blender method is very effective—put menstruum and chopped herb into a blender, and begin blending. Keep adding pieces of herb until the blender can take no more. This method produces a stronger tincture, but it is more difficult to squeeze the menstruum from at completion of the tincturing process.

In the industry, two main methods are used to make TRs and FEs: percolation and maceration.

Maceration:

Dried herb is soaked (macerated) in the desired menstruum at room temperature for a time. To prepare an herbal tincture, one should loosely fill a wide-mouthed glass bottle or jar with herbal parts. Plastic may be acceptable but could adsorb certain plant components, and metal should be avoided. If fresh herbs are used, they should be cut into manageable pieces. If dried herbs are used, they should be crumbled into the container. Pure spirits, such as vodka or a calculated ethanol:water combination, should be added to cover the herbs. The container should be sealed and the tincture allowed to stand in a warm place for 2 weeks. During the time that the tincture is maturing, the container should be shaken daily. After 2 weeks, the herbs (marc) should be strained out (in an herb press or a fine sieve, or wrapped in muslin by hand) and the residue squeezed out so that as much liquid as possible is retrieved. The final menstruum is allowed to settle, decanted and filtered through cheesecloth, a coffee filter, or laboratory filter paper. Dark glass bottles should be sealed well and stored out of direct sunlight. This process is suitable for small-scale production of tinctures and can easily be done in the practice. Fluid extracts can also be made by means of multiple maceration, a process that involves a series of macerations by which constituents are concentrated. For the home pharmacy, wine bottles are convenient for storage.

Percolation:

Ground dried herb is soaked in the menstruum (solvent) for several hours. The swollen plant material is then packed into a percolator, which is a tall metal or glass cylinder. More menstruum is added to cover the plant material, and this is left to macerate for 24 to 48 hours, and sometimes for weeks, depending on the herb. A tap at the bottom of the percolator is then opened to allow a slow drip, and the percolate is collected in a closed container. This process of simple percolation is suitable for the preparation of home tinctures. A number of complicated processes are used commercially to make more concentrated extracts.

Dilution:

Some manufacturers make very concentrated extracts by reducing the volume of liquid under partial vacuum, then diluting in another liquid. This usually involves heat; therefore, extracts made in this way are generally considered to be of inferior quality because of the potential for heat damage to some of the constituents. TRs and FEs made by diluting these concentrated extracts are therefore of poorer quality than those made by maceration or percolation.

Glycerin Extracts, Glycerites, and Glycetracts

Glycetracts use glycerin and water as solvents. They were traditionally made with mucilaginous herbs like marshmallow (Althea officinalis) and licorice (Glycyrrhiza glabra), but now many herbs are available in this form. The following is true of glycetracts:

• They are sweet tasting

• More palatable than alcohol extracts

• Sweet taste of glycerin may hide the taste of the herbs, but some herbs may taste bad enough that animals do not accept glycerin extracts readily

• Are dispensed in the same way as FEs and TEs

• Can be mixed with alcohol-based extracts

Fresh plant extracts are best used with glycerin because it is better at preserving fresh plant juice as opposed to extracting components from the plant cells. Glycerin extracts tannins well and may help protect them from precipitation in mixed alcohol tinctures. One limitation to using glycerin tinctures is the potential for microbial contamination, especially from fresh plant starting material. Glycetracts can be made through maceration or percolation, as described; however, glycerin is not as good a solvent as water or alcohol. This problem is overcome by the making of modern glycetracts by replacement.

Replacement

Replacement involves gentle heating of a fluid extract to evaporate off the alcohol (and sometimes water). When the desired volume is reached, glycerin is added to return the extract to its original volume.

Glycerites ideally should be kept capped and refrigerated because they can mould. Glycerin tinctures must consist of more than 55% pure glycerin if they are to have preservative capacity (vegetable glycerin contains 5% water, which must be factored into the calculation).

For herbs that are best extracted in glycerin (including mucilaginous herbs like marshmallow), generally 4 parts glycerin and 1 part water are used to extract the herbs. Glycerin can also be mixed with a small amount of alcohol for broader extraction and better preservation.

Vinegar Extracts

Vinegar may be added to alcohol, water, or glycerin tinctures to increase the extraction of certain constituents, especially alkaloids. Aceta are pure vinegar tinctures, and these are not as strong as alcohol tinctures.

Supercritical CO₂ Extracts

A newer type of concentrated herb extract is the supercritical carbon dioxide (CO₂) extract. CO₂ is generally recognized by the US Food and Drug Administration (FDA) as a safe solvent (GRAS). In this process, pressurized CO₂ gas is pumped into a chamber filled with plant matter. Pressurized CO₂ is very dense; it functions as a liquid and extracts lipophilic components from the herb. Reported advantages of supercritical CO₂ extracts include the following:

• They leave no chemical residue of their own in the extract

• No high temperatures are used, which means that plant constituents have not been heat stressed (extraction temperature is 95° F–100° F, as opposed to 140° F–212° F)

• They are environmentally safe, leaving no harmful residues that need disposal

• They are highly concentrated and require no preservation because water, proteins, and sugar required to support microbial growth are absent

The end result is a broad spectrum of lipophilic constituents in the herb, which also means that this is not the appropriate technology for all herbs.

Fresh Plant Extracts

Fresh plant tinctures (FPTs) are made from fresh rather than dried plants. Some herbalists prefer this because of the “vitality” aspect retained in the plant; in some cases, drying changes the chemistry of the herb, making it less useful. However, fresh plants are bulkier and contain more moisture; this means that more menstruum is needed to cover the material. Also, the water that is an innate part of the plant will add to the volume of the menstruum; therefore, it is difficult to make a concentrated extract of FPT.

By convention, the strength of FPT is based on the equivalent dried weight of the plant used, and the FPT product may state its dried weight equivalent (e.g., a 1 : 10 FPT is far less concentrated than a 1 : 10 liquid extract from dried herb). FDA regulations do not require that a dry equivalent must be stated on the label, however, which is sensible because no equivalent dried product may be available (e.g., in those cases where fresh plant extracts are more effective than dried plant extracts).

DISPENSING TINCTURES AND FLUID EXTRACTS

The beauty of stocking and dispensing TRs and FEs is that each is made from one species of medicinal plant and can be combined in limitless permutations, allowing for individualization of medicine according to patient needs.

In general, TRs and FEs can be mixed together with no problem. Some attention should be given to the relative alcohol percentages because these can affect the solubility of certain constituents. For example, mixing a mucilaginous extract with a high-alcohol extract causes the mucilage to precipitate out of solution and form a lump in the bottom of the bottle. Tannins and alkaloid extracts can also cause precipitation.

To remove some of the alcohol from a tincture, a suitable number of drops or volume of tincture must be added to 1 tablespoon of very hot water. Most of the alcohol evaporates away in about 5 minutes. This must be cooled and added to moist food.

Various flavoring agents can be used to improve palatability.

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Tags: Veterinary Herbal Medicine

Jul 18, 2016 | Posted by admin in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off

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