for bladder dysfunction and migraine prevention,
and claimed to be innocuous on grounds of chemi-
cal purity but without much biological, toxicologi-
cal testing. Similarly, oral melatonin has an
absolute bioavailability of about 15% maximum
and was eventually withdrawn in the United King-
dom and Japan after safety concerns arose
(DeMuroet al., 2000). The types and amounts of
degradants and impurities in these products are
unknown.
5.3 Formulation choice
The formulation chosen for particular drugs is not
random, but the degree to which it is critical varies
from drug to drug. For example, hydrocortisone is
available for at least sevenroutes of administration,
as tablets, several creams and ointments, intraocu-
lar solutions, suppositories, intrarectal foams,
injections and eardrops. Even newer drugs, with
fewer indications than hydrocortisone, seek greater
market acceptability by providing a variety of
alternative formulations (e.g. sumatriptan is avail-
able as an injection, intranasal spray, suppository
and tablets).
One commonly used principle is to target drug
delivery to the organ where beneficial effects are
likely to occur. This can achieve
relatively fast onset of effect;
locally high drug concentrations;
relatively low systemic drug concentration,
avoiding toxicity;
probably the most common applications of this
principle are the administration of beta-adrenergic
agonists bronchodilators by inhalation and the use
of topical hydrocortisone creams.
Formulation characterization
Various physicochemical properties of bulk drug
can be measured. Some will be reasonably familiar
from medical school biochemistry, for example the
one or more pK values for active drug or excipi-
ents, or the pH of drug solutions in specified aqu-
eous solutions. The log P is a measure of
lipophilicity, usually measured as the octanol/
water distribution coefficient when the aqueous
phase is buffered at pH 7.4. Powder density is the
ratio of weight and volume occupied by a powder;
some powder particles pack together more effi-
ciently; the familiar comparison between table
salt and talcum powder is an illustration. Particle
size and distribution is often measured using infra-
red devices. Maximum solubility (xmg ml^1 )in
various solvents is also often helpful not only to
those whose task is to make drugs into prescribable
pharmaceutical formulations but also to toxicolo-
gists estimating a maximum feasible dose in a
given species by a particular route of administra-
tion. Hygroscopicity is a measure of the capability
of a drug to absorb water from the atmosphere;
such drugs gain weight with time, are often less
stable than drugs lacking this property, and may
thus predicate an aluminium foil packaging. Stan-
dard manuals such asMerck Indexprovide many of
these data.5.4 Specific formulations
Oral formulationsinclude tablets, syrups, wafers
and suspension according to the excipients used.
Bindersare used to hold the various components
together, and examples would be starch or poly-
vinylpyrrolidine (to which dogs exhibit a species-
specific allergy).Bulking agents(sometimes called
dilutants, or, confusingly for a solid formulation,
diluents) include lactose and cellulose; these
increase tablet weight, which can improve produc-
tion uniformity. Silica and starch may also be used
to improve the flow of powder in mass production,
when they are known aspro-glidants.Stearic acid
salts are used to enable tablets to escape from the
press when finished, this being an unusual use of
the termlubricant.Coatingsare often sugars or
cellulose and may be employed when a drug tastes
foul. Particular color schemes can be created with
dyestuffs or iron oxide.
Most wafer formulations dissolve in the mouth
and are actually converted into a solution for5.4 SPECIFIC FORMULATIONS 53