Chemical Stability

What are the main types of drug instability?

Physical, microbial, and chemical.

What are key chemical degradation pathways?

Hydrolysis, oxidation, photochemical decomposition, polymerisation, and isomerisation.

What functional groups are susceptible to hydrolysis?

Esters, amides, lactones, lactams, sulfates, phosphates.

What factors affect ester hydrolysis?

pH, temperature, moisture content, solubility, and electronic/steric effects.

Why are β-lactam antibiotics unstable?

Strain in the four-membered ring reduces resonance stabilization, making the carbonyl more reactive.

Which metal ions catalyze β-lactam degradation?

Zn2+, Cd2+, Cu2+, Pb2+.

What is a Lewis acid?

A substance that accepts an electron pair.

What is a Lewis base?

A substance that donates an electron pair.

What defines oxidation?

Addition of oxygen, removal of hydrogen, or loss of electrons.

What is autoxidation?

Spontaneous oxidation involving reactive oxygen species (ROS) at ambient temperatures.

Examples of ROS?

Superoxide anion, hydrogen peroxide, hydroxyl radical, singlet oxygen.

Key reactions generating ROS?

Fenton reaction and Udenfriend reaction.

Which molecules are susceptible to oxidation?

Ethers, amines, phenols, aromatic amines, thiols.

How to minimise oxidation?

Protect from light, use chelators (e.g., EDTA), add antioxidants, use inert packaging gases.

Examples of antioxidants used?

Ascorbic acid, butylated hydroxytoluene (BHT), vitamin E, propyl gallate.

What is the role of colipase in lipid digestion?

Assists pancreatic lipase by binding to bile salts and allowing lipid hydrolysis (related note).

What happens when proteins are exposed to oxidation?

Methionine and cysteine residues are particularly susceptible.

What is the effect of hydrogen peroxide on sulfides?

Oxidation to sulfoxides via nucleophilic attack.

What is the impact of acidic pH on drug stability?

Drugs like phenols and thiols are more stable in acidic pH.

What functional groups can H2O2 react with?

Carboxylic acids, bicarbonate, nitriles, forming strong oxidizing agents.