chemical degradation

Chemical degradation is the drug molecule quietly falling apart over time, like iron rusting or a sliced apple browning. The active ingredient reacts and turns into different molecules — so a 500 mg tablet might, after years, deliver less than 500 mg of intact drug, plus some breakdown products that were never meant to be there.

It proceeds through definite chemical pathways, most often hydrolysis (water cleaving bonds), oxidation (reaction with oxygen or free radicals), and photolysis (light-driven breakdown). Others include isomerisation, decarboxylation, polymerisation and reactions between the drug and excipients. Each pathway has a characteristic rate that depends on temperature, pH, moisture, light and catalysts such as trace metals.

Degradation matters for two reasons: loss of potency (an underdose) and the appearance of degradation products, some of which may be toxic, immunogenic, or simply unattractive (discolouration, odour). Regulators therefore limit not only how much active must remain but also how much of each impurity is allowed.

Formulators fight degradation by choosing a stable salt or polymorph, buffering to the pH of maximum stability, drying the product, excluding oxygen and light, and adding antioxidants or chelating agents. What cannot be removed is managed by setting a conservative shelf life.