Hydrolysis: death by water
Hydrolysis is the most common degradation route, because water is almost everywhere — in solutions, in moist air, even trapped inside tablets. A water molecule attacks a weak point in the drug and splits it in two. The classic weak points are ester and amide bonds: aspirin (an ester) hydrolyses to salicylic acid and acetic acid; many antibiotics carry fragile rings or amides that water pulls apart.
Hydrolysis usually speeds up at very low or very high pH, because acid (H⁺) or base (OH⁻) catalyses the reaction. So a key defence is choosing the pH where the drug is most stable and holding it there with a buffer. This is also why ester-prone drugs are often sold as dry powders to be reconstituted just before use — keep the water away and the clock barely ticks.
Oxidation: death by oxygen
Oxidation is loss of electrons — usually a reaction with oxygen from the air. It tends to run as a chain reaction: once started, reactive fragments keep the process going on their own, which is why oxidation can show a long quiet period and then accelerate. Adrenaline turning pink, vitamins losing potency, and oils going rancid are all oxidation.
Because it is a chain, oxidation has several places to interrupt it. Remove the oxygen (flush the headspace with nitrogen). Add an antioxidant that sacrifices itself instead of the drug. And add a chelating agent to lock up trace metal ions like iron and copper, which act as catalysts even at parts-per-million levels. Guide 4 returns to these helpers in detail.
Photolysis: death by light
Photolysis is degradation driven by light energy. A photon is absorbed by the drug and supplies the push that breaks a bond or kicks off oxidation. Drugs that absorb in the UV or visible range — many with conjugated double bonds or aromatic rings — are at risk. Nifedipine, riboflavin and several antipsychotics are textbook light-sensitive examples.
The defence is simple in principle: keep light out. Amber glass, opaque plastic, foil blisters and outer cartons all help. Formally, a product's resistance to light is its photostability, and it is tested under defined light exposure so that the protective packaging can be justified rather than guessed.