Page 70 - Quality control of pharmaceuticals (07-PA 704)

Similarly, drugs that are salts of weak acids with strong bases are alkaline in solution
and the OH-produced by partial hydrolysis of the salt can act as a catalyst and bring
about decomposition. The mechanisms of acid – and base- catalysed hydrolysis of
esters are shown in the following figures.

Amide bonds are less susceptible to hydrolysis than ester bonds. The leaving group,
an amine, is a poorer leaving group. It involves cleavages of amide linkage to give
an amine instead of alcohol as in case of esters. This difference in the hydrolysis of
esters and amides is exemplified with lidocaine and procaine. The ester-containing
local anaesthetic procaine is now seldom used.

Although procaine is a good local anesthetic, its effect is short-lasting because its
ester group is rapidly hydrolysed. Conversely, lidocaine contains an amide bond,
which is less readily hydrolysed than procain's ester. As such, it is more stable to the
effects of hydrolysis and this, in addition to lidocaine's more bulky structure, makes
it a longer-acting local anaesthetic.
Amide-containing drugs;
As previously mentioned, amide-containing drugs are also susceptible to hydrolysis,
but it occurs at a much slower rate than the hydrolysis of esters. An example is the
hydrolysis of the stained cyclic-amide ring (amides that are part of a ring structure
are known as lactams) of − antibiotics.

Prodrug strategy:
Salicylic acid is a good painkiller. However, the presence of the bare alcohol moiety
causes gastric bleeding. Such an effect is overcome by masking this alcohol group
as an ester, which is later hydrolysed in the body to free the active drug. Such an