Drug delivery
Delivering drugs via the inhalation route was among the topics covered
at drug delivery sessions in
honour of Professor Bob Davis on September 15. Gareth Jones, editor of Hospital
Pharmacist, reports
Inhaled insulin heralds new preparations The world is waiting for inhaled insulin to become available before
further significant sums are put into research for other systemically
absorbed pulmonary dosage forms, said Professor Peter Byron from Virginia
Commonwealth University, Virginia. Several insulin inhaler devices are
now in phase III clinical trials. It is possible to get reproducible
absorption with inhaled insulin. The bioavailability is around five per
cent relative to intravenous administration. However, there is currently
a delay in inhaled insulins becoming available while the manufacturers
complete toxicological studies.
Many researchers have shown that with animal models, good absorption
of inhaled macromolecules can be achieved, said Professor Byron. In rat
studies, 50 per cent bioavailability has been achieved via the intratracheal
route. A longer half-life than with intravenous administration is seen
due to slow rates of absorption from the lung. With this slow rate of
absorption, ciliary clearance can be a problem as it is clearly likely
to reduce overall absorption. Therefore, when delivering macromolecular
drugs to the lung, with the aim of achieving systemic absorption, it
is necessary to deliver the drug to the pulmonary or alveolar region
where there is much slower clearance than in the upper airways. Professor
Byron pointed out that the devices that are being developed to deliver
insulin will need to be far more efficient than asthma delivery devices
if systemic absorption is to be achieved.
For the successful development of marketable products for pulmonary drug
delivery, good devices and formulations need to be developed. Alveolar
transporters may also be developed which will improve the degree and
speed of absorption, Professor Byron added.
He then moved on to local drug delivery to the lung, where there have
been shake-outs in the market in the past ten years.
A good inhaler device for local delivery to the lung should have the
following properties: reproducible aerosol size/dose, not contain chlorofluorocarbon
propellants, have a good shelf life, be easy to use, be cheap and offer
multiple new and old drugs in similar formats. There are many examples
of these products on the market, although they are not efficient.
Some of the formulation challenges still present, he said, include achieving
reproducible delivered doses and aerosol size distribution throughout
the life of a multidose preparation, avoiding the change in delivered
doses that can occur in suspensions, preventing suspended materials from
being expelled onto the internal container surfaces and dealing with
partial drug solubility which often leads to crystal growth. |
