For example, the dry-powder inhaler was initially
devised for sodium cromoglycate (which is almost
insoluble), but it is now also helping to solve the
metered-dose inhaler with hydrofluorocarbon pro-
pellant problem. The intravenous emulsion of pro-
pofol was unique, again being invented out of
necessity, but is now also used for antifungal
agents. There are several other examples of truly
unique formulations or routes of administration
that we may expect to be further exploited in the
future. AIDS-associated infective retinitis is trea-
ted with a drug administered by intraocular injec-
tion, and the current parlous state of retinal
detachment treatments suggests that this route of
administration may find wider use.
What are we likely to see in the future? Novel
pharmaceutical formulations seem to fall into two
groups, those being used forgene therapy and those
being used elsewhere.
Investigational gene therapies are comprised of
two components: the DNA itself (the ‘construct’)
and usually a method of delivery (‘the vector’).
Naked DNA can be injected but its expression is
inefficient. Vectors may include viruses. However,
such viruses have to be human, and their attenua-
tion sometimes is lost after administration, leading
to very serious adverse events. Nonviral vectors
can include targeted liposomes, microspheres and
emulsions.
Needleless injectors have been available for
decades, yet still seem to be underused (the needle-
less injector used by Dr ‘Bones’ McCoy of the
‘USS Enterprise’ is clockwork, develops several
thousand pounds pressure per square inch, and
feels like a mild middle-finger percussion when
used over the deltoid). It turns out that cell mem-
branes become transiently leaky when exposed to
high voltages: otherwise insoluble or excluded
drugs can enter the cell under these conditions,
and the device that performs this is known as an
electroporator.
5.7 Summary
The objective of this chapter has been to provide
someappreciationofthecomplexityofpharmaceu-
tical development. Understanding the vocabulary
will help participation in team meetings where
pharmaceutical and clinical development must be
coordinated. A chapter on this scale will never
equip the generalist to conduct pharmaceutical
development. But, at the very least, it should now
be clear that a drug is not a drug is not a drug.References
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