B: Rational Phytotherapy A Physicians' Guide to Herbal Medicine

by V. Schulz R. Hansel, v. E. Tyler


Notes:

As a general rule, the equivalent dosage of an herbal product compared with
a traditional single dose taken in a cup of medicinal tea would be in the range of
200-500 mg of crude extract. Large capsules or coated tablets are the only practical
means of delivering such a dose.


Herbals were still based on classical humoral
pathology, which taught that health and disease were determined by the
four bodily humors - blood, phlegm, black bile, and yellow bile. The humors, in
turn, were associated with the elemental principles of antiquity: air, water, earth,
and fire. The elements could be mixed in varying ratios and proportions to produce
the qualities of cold, moist, dry, or warm - properties that also were associated
with various proportions of the four bodily humors. Thus, if a particular disease
was classified as moist, warm, or dry, it was treated by administering an herb
having the opposite property (Jiittner, 1983). Plant medicines were categorized by
stating their property and grading their potency on a four-point scale as "imperceptible:'
"perceptible:' "powerful:' or "very powerful:' Opium, for example, was
classified as grade 4/cold. A line of association that linked sedation with "cooling" allowed
the empirically known sedative and narcotic actions of opium to be fitted into
the humoral system. Pepper was classified as grade 4/dry and warming. The goal of
all treatment, according to Hippocrates, was to balance the humors by removing
that which is excessive and augmenting that which is deficient" (H. Haas, 1956). Humoral
pathology obviously developed into one of the basic principles of conventional
medicine.


Cardiac glycosides of the digitalis type have a very narrow range of therapeutic
dosages. Exceeding the full medicinal dose by just 40 % can produce toxic effects.
The dosage problem is compounded by the large qualitative and quantitative variations
that occur in the crude plant material. Depending on its origin, the crude
drug may contain a predominance of gitoxin, which is not very active when taken
orally, or it may carry a high concentration of the very active compound digitoxin.

Thus, isolating the active constituents from herbs with a narrow therapeutic
range (Fig. 1.1) and administering the pure compounds is not simply an end in itself.
This scientific method of medicinal plant research is, rather, the means by which
very potent constituents can be processed into safe medicinal products. The goal is
not to concentrate the key active component but to obtain a pharmaceutical product
that has a consistent, uniform composition. Processing the isolated constituent into
pills, tablets, or capsules results in a product that is diluted by pharmaceutical excipients.
For example, the concentration of digitoxin in a digitoxin tablet is approximately
10 times lower than in the original digitalis leaf.



Phytomedicines: Phytomedicines are medicinal products that contain plant materials as their pharmacologically active component. Keller (1996) may be consulted for an up-to-date
overview of experiences with herbal drug products in Germany and Europe. For
most phytomedicines, the specific ingredients that determine the pharmacologic activity
of the product are unknown. The crude drug (dried herb) or a whole extract
derived from it is considered to be the active ingredient. Thus, phytomedicines are
complex mixtures of compounds that generally do not exert a strong, immediate action,
and whose effect would be classified as imperceptible to perceptible in the historical
grading system. Due to the large part of patient and consumer expectations
(see Sect.1.5.5), it is essential that phytomedicines in the strict sense have a wide
margin of safety. Most liquid dosage forms are produced from fluidextracts, and
most solid dosage forms are solid extracts. Relatively few herbal drug products are
made with powdered herbs or oil distillates


What are Extracts?
Extracts are concentrated preparations of a liquid, powdered, or viscous consistency
that are ordinarily made from dried plant parts (the crude drug) by maceration or
percolation. Fluidextracts are liquid preparations that usually contain a 1: 1 ratio of
fluidextract to dried herb (w/w or v/w). Ethanol, water, or mixtures of ethanol and
water are used exclusively in the production of fluidextracts. Solid or powdered extracts
are preparations made by evaporation of the solvent used in the production
process (raw extract). Further details on pharmaceutical preparation and extraction
techniques for herbal medications are shown in Fig. 1.2.
In some cases it is necessary to remove unwanted components from the raw extract
and increase the concentration of the therapeutically active ingredients. Standardized
ginkgo powdered extract (50: 1) is an example of this process. The 50: 1 ratio
means that, on average, 50 parts of crude drug must be processed to yield 1 part
extract. Potentially allergenic ginkgolic acids are eliminated from the extract along
with pharmacologically inert substances.
Volatile oils are also concentrates of active plant constituents. They are generally
obtained by direct distillation from the crude drug material or, less commonly, by lipophilic
extraction. The ratio of herb to concentrate (known technically as the HER,
or herb-to-extract ratio) for volatile oils is usually in the range of 50: 1 to 100: 1 (wI
v), corresponding to a volatile oil content of 1-2 % in typical herbs that contain
such oils.


1.4.1.1
Tinctures, Glycerites, and Related Products
Tinctures are alcoholic or hydro alcoholic solutions prepared from botanicals. If glycerol
is used as a solvent, the preparation is known as a glycerite. Increasingly, extractions
are performed with a mixture of glycerol, propylene glycol, and water instead
of ethanol and water. Polyethylene glycol 400 has recently been used as a solvent.
Glycerol is a physiologic substance, occurring as a component of natural glycerides.
Propylene glycol is a form of glycerol in which one of the two terminal hydroxyl
groups is absent. Polyethyleneglycol is a synthetic product, the number 400
indicating its average molecular weight. It is a clear, colorless liquid that preferentially
extracts lipophilic compounds from the crude drug.
The type of solvent used is indicated by the manufacturer; for example, it may appear
on the package insert under the heading "Other Ingredients" or "Excipients:'
There are two methods of producing fixed combinations in tincture form: by mixing
individual tinctures or by mixing the crude drug and then performing the extraction.
The difference is illustrated by two similar prescription formulas that are used
in the treatment of indigestion:
Prescription 1:
Rx Compo cinchona tincture 100 mL
Directions: Take 30 drops, diluted with water,
three times daily shortly before meals.
The preparation is made by extracting an herbal mixture composed of cinchona
bark (12 parts), bitter orange peel (4 parts), gentian root (4 parts), and cinnamon
bark (2 parts) with 70% ethanol (v/v) (100 parts).
Prescription 2:
Rx Cinchona tincture 60.0
Bitter orange peel tincture 20.0
Gentian tincture 20.0
Cinnamon tincture 10.0
Directions: Take 30 drops, diluted with water,
three times daily shortly before meals.
The pharmacist makes up this prescription by mixing the ready-made tinctures. The
preparation may become cloudy or form precipitates, but generally this will not alter
its efficacy. One advantage of liquid dosage forms in general is that they provide an
alternative for patients who have difficulty swallowing pills and capsules. One disadvantage
is their shorter shelf life, which may be further reduced due to improper
storage by the patient (open container, too much heat or moisture).
1.4.1.2
Syrups
Already known to ancient Arabic healers, medicinal syrups entered European medicine
during the early Middle Ages. The word syrup is derived from the Arabic sirab,
scharab or scherbet, meaning a sugary juice beverage. Syrups are viscous preparations for internal use containing at least 50 % sucrose and usually 60-65 %. The sugar
content of syrups (about 66 %) is essential for extending their shelf life. Microorganisms
cannot proliferate in saturated sugar solutions because highly concentrated
solutions deprive the microbes of the water necessary for their development. Preservatives
must be added to syrups with a lower sugar content to protect them from
bacterial growth.
Syrups are used as flavoring agents, especially in pediatric medicine. Marshmallow
syrup, fennel syrup, English plantain syrup, and thyme syrup are all commonly
prescribed herbal syrups.
1.4.1.3
Medicinal Oils
Medicinal oils are mostly fatty oils or liquid waxes containing solutions or extracts
of drug substances. Medicinal oils are used both internally and externally. Examples
of medicinal oils prepared by extraction of plant material are St.John's wort oil and
garlic oil maceration. Oils containing dissolved drugs are exemplified by solutions
of volatile oils in liquid jojoba wax, which are commonly used as massage oils, especially
in aroma therapy.
1.4.1.4
Medicinal Spirits
A spirit or essence is a solution of a volatile substance in alcohol or in water and alcohol.
Medicinal spirits are made either by dissolving the volatile oil in alcohol, as in
the case of Peppermint Spirit BPC made with peppermint oil, or by distillation.
To produce a medicinal spirit by distillation, the crude drug is pulverized, mixed
with alcohol, and allowed to stand until the volatile components have dissolved out
of the herbal tissue (oil cells, oil glands, oil reservoirs). Finally these components
are recovered by distillation.
There is an inherent risk of dependency in the use of medicinal spirits, which
may reactivate an old alcohol-related illness or exacerbate an existing one.

1.4.1.5
Plant Juices
Freshly harvested plant parts are macerated in water and pressed. The shelf life of
the expressed juice can be extended by conventional pasteurization or by rapid, ultra-
high-temperature treatment (flash method). Plant juices are produced only
from medicinal plants that do not contain highly potent chemicals. While expressed
juices do contain the water-soluble components of the processed plant, they are free
of lipophilic constituents. Little is known about the chemical composition of plant
juices or their possible reactions in aqueous media. Plant juices are over-the-counter
remedies that are used chiefly for self-medication.
Some common sources of plant juices are birch leaves, nettle, watercress,
St. John's wort, garlic, dandelion, lemon balm, European mistletoe, radish, English
plantain, and horsetail

Solid Dosage Forms
Powdered extracts and concentrates must be protected from light, oxygen, and
moisture. This is best accomplished by processing them into solid dosage forms
such as granules, tablets, coated tablets, and capsules. Preparing medications in a
form appropriate for their intended use also permits more accurate dosing. In addition
to solid dosage forms, there are other forms such as tinctures of fluidextracts,
ampules, and semisolid preparations. This section deals exclusively with solid dosage
forms. A drug substance becomes a medication through the process of pharmaceutical
formulation, in which excipients are added to the drug substance. Physicians
can easily access product information to learn about the excipients that have
been used in any given product. Solid dosage forms must be taken with an adequate
amount of liquid (100-200 mL) to avoid leaving drug residues that may harm the
esophagus. This is a particular concern in the elderly and in patients with preexisting
damage to the esophageal mucosa (alcohol).
1.4.2.1
Granules
Granules are aggregates of powdered material held together with binders. Their production
involves the use of various excipients such as gelatin solution, methyl cellulose,
povidone, simple syrup, lactose, and sucrose. Granules are usually processed
into tablets but also may be used as a separate dosage form. Drug substances used
in the treatment of gastrointestinal complaints are often produced in granulated
form.
1.4.2.2
Uncoated Tablets
Tablets are made by the compression of powdered or granulated material (compressed
tablets). Besides the active ingredients, which may amount to only a few milligrams,
tablets contain diluents, binders, lubricants, coloring and falvoring agents,
and desintegrators to help the compressed tablet dissolve in an aqueous medium.
1.4.2.3
Coated Tablets
Coated tablets are compressed tablets covered with a coating of sugar, dyes, fat, and
wax. The function of the coating is to protect the medicinal core. Tablets can also be
coated with film-forming agents, usually polymers (e.g., cellulose acetate phthalate),
to produce a film-coated tablet (PCT). Several advantages of coated tablets are indicated
below:
Release of the medication can be controlled or delayed (enteric-coated tablets,
controlled-release tablets).
• Shelf life is extended, as the coating protects against external influences such as
light, moisture, and mechanical stresses.
• They are easier to swallow than uncoated tablets.
• The coating masks any unpleasant taste from the medicinal core.

1.4.2.4
Capsules
Hard gelatin capsules consist of a two-part cylindrical shell whose halves are fitted
together after the medication - a powdered or granulated drug substance - has
been placed inside. Besides gelatin, the capsule shell contains glycerin or sorbitol
as a softening agent, water, aromatics, dyes, and antimicrobial additives. Volatile
oils may be encapsulated by adding them first to a powdered excipient; the oils will
subsequently be released in the gastrointestinal tract.
Soft gelatin capsules are spherical, oval, oblong, or teardrop-shaped capsules with
a gelatin shell enclosing semisolid or liquid contents that must be free of water (e. g.,
oily garlic extracts or peppermint oil).
The material of the capsule shell can be designed to delay the release of the drug
substance until the capsule has entered the stomach or intestine. A chemically modified
cellulose, hydroxypropylene methylcellulose phthalate (HPMCP), makes an effective
enteric (gastric-acid-resistant) coating. Insoluble while in the acidic milieu
of the stomach, this compound dissociates when the pH rises above 7 and becomes
soluble under physiologic conditions.
Enteric coatings on capsules and tablets offer several advantages:
• They protect the drug substance from deactivation or decomposition by gastric
juices .
• They shield the stomach lining from drug substances that could cause irritation
or nausea (salicylates, emetine) .
• They prevent dilution of the drug substance before it reaches the bowel (intestinal
antispasmodics or antiseptics).
Enteric-coated capsules or tablets that release the drug substance after entering the
bowel should never be taken during or after meals, but approximately 1 hour before
meals.
Particles larger than 3 mm in diameter do not leave the stomach with the chyme;
they are retained in the stomach until the subsequent interdigestive phase. One danger
of enteric-coated capsules is that they may remain in the stomach for some time
while the pH of the gastric juice rises, leading to premature release of the drug inside
the stomach.
1.4.2.5

Lozenges
Lozenges (troches, pastilles) have a tablet-like appearance (round, oblong, etc.) but
differ from tablets in that they are not made by compression but are molded or cut
from pliable masses of varying composition. Lozenges are designed to release the active
ingredient slowly into the oral cavity while sucked or chewed. The base is composed
of sucrose (usually more than 90 %), acacia (about 7 %), gelatin, tragacanth,
and water (e.g., Echinacea Capsettes).

1.6.5
Teas Compounded as Prescribed by a Physician
Common abbreviations: cort. (cortex, bark); fo!' (folium or folia, leaf or leaves); fret. (fructus,
fruits) ; pericarp. (pericarpium, peel); rad. (radix, root); rhiz. (rhizome); sem. (semen or semina,
seed); stip. (stipes or stipites, stem); summ. (summitates, branch tips); tub. (tuber or tubera).
Historically, the prescription written by a physician consists of six parts (Bader et at.,
1985).
1. The heading contains the name and academic degree of the prescriber, the prescriber's
address, telephone number and professional title (e.g., general practitioner),
and the date on which the prescription is written.
2. The superscription, written Rx, is the symbol for the Latin word recipe (take) and
directs the pharmacist to prepare the medication.
3. The prescription (or inscription) lists the ingredients and states their individual
quantities relatively (in parts) or absolutely (in grams). Usually the total quantity
of the prescription is 100 g. The various ingredients of the prescription have different
functions and may consist of four distinct parts .
• The base, or chief active ingredient, such as a bitter herb in an appetite-stimulating
stomach tea.
• The adjuvant, or supportive medicine, that acts in the same manner as the base,
such as an aromatic bitter in a stomach tea.