Examples of drugs susceptible to hydrolysis

Diamorphine injection is prepared by dissolving the contents of a sealed container in Water for Injections BP immediately prior to use. The instability of the ester groups precludes sterilisation of the injection by autoclaving. 

A close inspection of the structure of diamorphine will show that the molecule also contains benzylic hydrogen atoms, on the CH2 adjacent to the benzene ring. This site is susceptible to oxidation and, for this reason, diamorphine should be stored in a well-closed container protected from light. 

Penicillin (and, for that matter cephalosporin) antibiotics are cyclic amides and are very prone to hydrolysis. Normal amide bonds are more resistant to hydrolysis than are esters, but in penicillins the amide is cyclised into a four-membered P-lactam ring. The bond angles in this ring are close to 90°, in contrast to an open-chain amide in which the bond angle is 120° (sp2 hybridised carbon). This unnatural bond angle in the P-lactam ring means that the ring is very easily opened by nucleophiles, particularly water. 

The effect is compounded by the geometry of the fused bicyclic ring system. The P-lactam and thiazolidine rings of penicillin do not lie in the same plane (in fact, they lie almost perpendicular to each other), so resonance effects within the cyclic amide are prevented, which leaves the carbonyl carbon atom much more 5+ than expected and hence more liable 

Penicillin and cephalosporin antibiotics are insufficiently stable to be supplied dissolved in aqueous solutions. Instead, they are supplied as a dry powder, which is reconstituted immediately prior to dispensing by the pharmacist. The solution (or, more accurately, suspension) dispensed must be stored in a refrigerator and discarded after 7 days. The ring-opened product (penicilloic acid) is inactive as an antibiotic. 

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Essentials of pharmaceutical chemistry Examples of drugs susceptible to hydrolysis... 

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