When a new drug product is being formulated, it is desirable to determine
the stability of the drug entity in the drug product so that a shelf life
or expiration date may be assigned to the product. The shelf-life is the
length of time required for the product potency to be reduced to some percentage
of its original value. For most products, this is the T90 or time at which
the product retains 90% of its original potency. Although the drug's stability
at room temperature is of primary interest, a stability study at room temperature
would take too long to be useful as a screening procedure for new formulations.
Therefore, such screening studies are conducted at elevated temperatures
in accordance with the Arrhenius equation:
The Arrhenius equation can be rewritten as:
Again, an equation of the form y = mx + b is generated, indicating that
a semi-log plot of Kapp vs. the reciprocal of the absolute temperature
(1/T) should yield a straight line with a negative slope equal to -Ea/R.
This line can be extrapolated to the value of 1/T that corresponds to room
temperature and the predicted rate constant for the reaction at room temperature
can be taken from the y- axis.
Although the degradation of aspirin in a solution buffered at pH = 7.5
occurs too slowly at room temperature to be adequately studied during one
laboratory period, the reaction proceeds rapidly at temperatures of 50°C
and above. The reaction will be conducted at approximately 55°, 60°,