hydrolysis

Hydrolysis is degradation by water: a water molecule wedges into a chemical bond and splits the drug in two, much as soaking a paper bag eventually tears it apart. Because water is everywhere — in solutions, in humid air, even trapped inside tablets — hydrolysis is the single most common way drugs break down.

It strikes molecules with water-cleavable bonds, above all esters and amides (and related groups such as lactams, lactones and carbamates). Aspirin (an ester) and penicillins (a beta-lactam) are textbook victims. The reaction is usually catalysed by hydrogen or hydroxide ions, so its rate depends strongly on pH; plotting rate against pH gives a characteristic curve with a minimum at the pH of maximum stability.

Because temperature, pH and water activity drive the rate, formulators counter hydrolysis by buffering to the most stable pH, by drying the product or supplying it as a powder for reconstitution just before use, and by using moisture-barrier packaging with desiccants. For very labile drugs, a freeze-dried (lyophilised) solid reconstituted at the bedside avoids storing the drug in water at all.

A caveat: lowering water content slows but rarely abolishes hydrolysis, because even a solid product holds residual moisture and excipients can carry their own bound water. The reaction merely becomes slow enough to fit within an acceptable shelf life.