by the American Chemical Society for release at 8 p.m. MDT (7 p.m.
PDT) Weds. April 4, 2001. Long will present the study during a 7-10
p.m. PDT Weds. April 4 poster session in the San Diego Convention
Centers Sails Pavilion.
April 4, 2001 – University
of Utah chemists have devised a quick way for pharmaceutical
companies to estimate the shelf lives of new medicines.
going to help drug companies decide which formulations of new medicines
are most stable and have the longest shelf life, said Chuck
Wight, a professor of chemistry.
T. Long, a postdoctoral research associate at the University of
Utah, was scheduled to outline the new method April 4 during the
American Chemical Societys national meeting in San Diego.
He conducted the study with Wight; Sergey Vyazovkin, a research
associate professor; and Nicoleigh Gamble, a former Utah undergraduate
now in medical school elsewhere.
study tested the technique on pure acetylsalicylic acid, the active
ingredient in aspirin. Like other organic substances, aspirin decomposes
with time. Heat accelerates the drugs breakdown.
Long and Wight
said drug companies normally test the shelf life of a new medication
by letting it sit for many months at 30 degrees Celsius (86 degrees
Fahrenheit) somewhat above room temperature and seeing
how long it takes for 5 percent of the medication to break down.
Right now, it is a very time-intensive and expensive process
to do these determinations, Long said. It can be a two-year
experiment to determine decomposition.
Such tests have
showed 5 percent of aspirin decomposes in about two years. The Utah
method which involves heating aspirin at a variety of temperatures
or heating rates while its decay is measured came up with
a shelf-life estimate of 2.4 years.
tests of a drugs stability, we can get an estimate of
shelf life on the order of days, Long said.
Long said using
such high heats to speed decomposition of a drug is clearly
much different than what happens in your medicine cabinet,
but produces estimates of room-temperature shelf life that agree
reasonably well with measurements based on letting the drug slowly
decay at near-room temperatures for months.
Wight said if
a drug company was developing a new medicine that had five possible
chemical formulations of equal or similar effectiveness, the test
could quickly determine which formulations were most stable and
thus would have longer shelf lives. Then the more conventional shelf-life
measurements could be done on those formulations.
is not to replace conventional room-temperature determinations of
shelf life, but to help screen out less stable drugs first,
The Utah chemists
have started discussing the new test method with drug company representatives,
but so far theres only been a mild amount of interest
because there are a lot of mathematics and analysis that go into
the method, Wight said. This paper is a proof-of-concept
which we hope to use in the future to get more people interested.
Wight said chemists
have known for a long time that a drugs shelf life can be
estimated by using heat to accelerate its decomposition. But the
method of extrapolating such experiments has, in the past, given
poor estimates of a medications shelf life at room temperature,
What we did is find a way of taking eight experiments [each
involving heating a drug at different temperatures and rates] and
analyzing them simultaneously to get a better prediction of shelf
life, Wight said.
By watching a drug decompose, the chemists determine kinetic
equations that can be used to calculate the medicines
shelf life at room temperature.
Long and colleagues
used two methods in their study. Both techniques involved placing
a tiny sample of pure aspirin in a quarter-inch-wide pan that is
then put inside an instrument that includes a small furnace to heat
a differential scanning calorimeter, measures the release or absorption
of heat produced by chemical decomposition of the medication as
it is heated, for example, from 25 to 600 degrees Celsius (77 to
1,112 degrees Fahrenheit). The other instrument uses what is called
thermogravimetric analysis, which measures how the medication
decreases in mass as it breaks down.
The latter method
proved simpler for making measurements used to estimate shelf life,
Long said. But both methods showed aspirin decomposes in two steps.