nasal sprays and aerosols. While the intent of this
guideline is to facilitate the development of generic
products for use by this route of administration, it
has been challenged on several scientific and tech-
nical grounds (e.g. Harrison, 2000).
Transdermal and topical formulations
The principal distinction between transdermal and
topical drugs is that only the former is intended for
systemic delivery. Both are subject to the same skin
irritancy testing prior to human exposures; precli-
nical and clinical skin irritancy testing is reason-
ably stereotypical and commodity priced.
Biologically, the skin is designed to be a barrier.
Evading this barrier is not easy, because drugs must
traverse both live dermis and dead epidermis. Lipo-
philic drugs tends to form a reservoir in the former,
even after traversing the hydrophobic latter. As in
oral transmucosal administration, potent drugs,
with modest requirements for mass absorbed and
reasonable lipophilicity, are the best candidates for
transdermal delivery. Fentanyl, nicotine and sco-
polamine are good examples.
Suppositoriesare probably the clearest illustra-
tion of cross-cultural differences in pharmaceuti-
cals. A surgeon on a famous ocean liner has
commented that ‘Part of the problem stocking
one’s pharmacy is that one needs three times as
many products as when working on land: Tablets
for the Brits, shots (injectables) for the Yanks, and
suppositories for the French!’
However, this route of administration is emi-
nently logical, in several circumstances. For the
acute treatment of migraine, oral drugs are often
vomited (sumatriptan). For treating acute asthma,
children often cannot use an inhalational device
properly (theophyliine). For perioperative antibio-
tics, patients are often nil by mouth (metronida-
zole). For inflammatory bowel disease and
proctitis, this is simply a topical administration.
Diazepam and paraldehyde administered rect-
ally are effective for terminating a seizure, espe-
cially in children, without the need to find a vein.
Use a glass syringe for paraldehyde.
Vaginal pessariesare suppositories designed for
a more acidic environment than that found in the
rectum. Topical uses include treatments forCan-
dida albicans, andTrichomonasinfections, as well
as for preparation of the cervix prior to induction of
labor. Contraceptive devices are outside of the
scope of a chapter on pharmaceutics, although
the nonoxyl containing sponge pessary is a unique
formulation. At the time of writing (May 2006),
there is controversy over whether mifepristone
is associated with greater clinical hazard when
administered per vagina in comparison with
being swallowed.Injectates (s.c., i.m, i.v.)
The solubility of a drug and the compatibility of a
particular solvent with the site of injection are
interrelated factors governing the suitability of
this route of administration and the pharmaceutical
formulation that is employed. The route of admin-
istration may also be governed by tolerability
aspects associated with the formulation. If a drug
cannot be dissolved in a concentrated manner in a
suitable vehicle, then often dose size must
increase. For example, intravenous injections of
penicillin-type antibiotics are much more comfor-
table than when the same dose is administered
intramuscularly.
Intravenous formulations are probably the least
demanding of all injectates; the humanvein is quite
robust, although venous irritancy is often encoun-
tered in clinical trials. A surprising example of this
robustness is seen when inducing anesthesia with
thiopental sodium (sodium thiopentone). The
upper limb veins tolerate these alkaline solutions
with impunity, but the solutions are very damaging
when administered occasionally and iatrogenically
into the cubital fossa; a solution at pH 9 can cause
serious injury to the structures at the elbow, includ-
ing the median nerve.
Organic solvents are often used to enhance the
rate of absorption from subcutaneous or intramus-
cular sites of administration. For example, benzyl
alcohol and sodium benzoate are used to dissolve
diazepam, and extravasation of this formulation is
not as serious a problem as for thiopental.
Water-soluble drugs are usually also hygro-
scopic. If not shipped and stored as solutions,58 CH5 PHARMACEUTICS