Chemistry Reference
In-Depth Information
8
Stability of drugs and medicines
Drugs sometimes have quite complicated chemical structures and are, by
definition, biologically active compounds. It should not, therefore, come as
a surprise that these reactive molecules undergo chemical reactions that
result in their decomposition and deterioration, and that these processes
begin as soon as the drug is synthesised or the medicine is formulated.
Decomposition reactions of this type lead to, at best, drugs and medicines
that are less active than intended (i.e. of low
efficacy
); in the worst-case
scenario, decomposition can lead to drugs that are actually toxic to the
patient. This is clearly bad news to all except lawyers, so the processes of
decomposition and deterioration must be understood in order to minimise
the risk to patients.
There are almost as many ways in which drugs can decompose as
there are drugs in the
British Pharmacopoeia
, but most instability can be
accounted for by the processes of
oxidation
and
hydrolysis
.
Oxidation
Oxidation is the process whereby an atom increases the number of bonds it
has to oxygen, decreases the number of bonds it has to hydrogen, or loses
electrons. The deterioration of drugs by oxidation requires the presence of
molecular oxygen and proceeds under mild conditions. Elemental molec-
ular oxygen, or O
2
, possesses a diradical (unpaired triplet) electronic config-
uration in the ground state and is said to be
paramagnetic
(a species with
all its electrons paired is called
diagmagnetic
). The structure of oxygen can
be represented as
.
O
O
.
O depending on whether the molecular
orbital or valence bond theory is employed. The important fact for drug
stability is that the radical species possesses two unpaired electrons, which
can initiate chain reactions resulting in the breakdown of drug molecules,
particularly if the reaction occurs in the presence of catalysts such as light,
heat, some metal ions and peroxides. The types of drugs that are affected
include phenols (such as morphine), catecholamines (for example,
adrenaline (epinephrine) and noradrenaline (norepinephrine)) as well as
polyunsaturated compounds such as oils, fats and fat-soluble vitamins (e.g.
or O
b
b
