Chemistry Reference
In-Depth Information
9
Kinetics of drug stability
The routes of decomposition of drugs, and the steps taken to prevent them,
were considered in Chapter 8. In this chapter the rates of decomposition
will be studied and useful information, such as shelf-life, will be predicted.
Calculations of this type are important as there is little merit in producing
the latest wonder drug designed to cure all ills only to watch it fall apart on
the dispensary shelf as a result of decomposition.
Rate, order and molecularity
The underlying principle on which all of the science of kinetics is built is the
law of mass action introduced in Chapter 1. This states that the rate of a
chemical reaction (i.e. the speed of the reaction or, simply, how fast it is) is
proportional to the active masses of the reacting substances. Active mass is
a complicated term to measure, but, fortunately, if the solutions in question
are dilute, the active mass may be replaced by concentration, which is much
easier to handle. If the concentration of a solute is greater than about
0.1 mol L
1
, significant interactions arise between the solute molecules or
ions. In cases like this, effective and measured concentrations are not the
same and use must be made of
activity
instead of concentration.
The
rate
of a chemical reaction is, in a dilute solution, proportional to
the concentrations of the various reactants each raised to the power of the
number of moles of the reactant in the balanced chemical equation. This
sounds too easy, and in fact it is. In practice, the rate of a chemical reaction
depends only on a small number of concentration terms, and the sum of the
powers to which these concentrations are raised is termed the
order
of the
reaction. This is because chemical reactions occur in a number of steps, or
stages (called a
mechanism
) and the rate of the overall reaction is often
governed by the rate of the slowest step (called, not surprisingly, the
rate-
determining step
). Even if every other stage of a chemical reaction occurs
essentially instantaneously, the rate of the reaction as a whole cannot
exceed that of the slowest stage.
For example, if the rate of a chemical reaction depended only on the
concentration of compound A, this could be written as
