Oxidation – stabilization of drugs MCQs With Answer

This set of MCQs covers oxidation and stabilization of drugs, a vital topic in pharmaceutical chemistry for B.Pharm students. It explains oxidation mechanisms — free radical initiation, propagation and termination — oxidative pathways, metal-catalyzed reactions, photoxidation, and peroxide formation in excipients. Stabilization strategies include antioxidants (primary and secondary), chelators, inert-gas blanketing, pH control, proper packaging, and formulation approaches like lyophilization. You will review kinetic concepts, analytical tests (peroxide value, iodometric titration), and regulatory stability considerations. Questions emphasize practical prevention, selection of excipients and antioxidants, and interpretation of stability data to ensure drug safety and shelf life. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary chemical definition of oxidation as applied to drug molecules?

• Gain of electrons
• Loss of electrons or increase in oxidation state of drug molecules
• Formation of covalent bonds
• Change in stereochemistry only

Correct Answer: Loss of electrons or increase in oxidation state of drug molecules

Q2. Which sequence correctly describes the free radical chain autoxidation mechanism?

• Termination → Propagation → Initiation
• Propagation → Initiation → Termination
• Initiation → Propagation → Termination
• Initiation → Termination → Propagation

Correct Answer: Initiation → Propagation → Termination

Q3. Which event typically represents the initiation step in autoxidation of a drug?

• Combination of two radicals
• Hydrogen abstraction from the drug forming a drug radical
• Formation of drug–oxygen adduct by radical recombination
• Reduction of drug by an antioxidant

Correct Answer: Hydrogen abstraction from the drug forming a drug radical

Q4. Propagation in radical chain oxidation usually involves which interaction?

• Drug radical reacting with oxygen to form peroxy radical
• Two antioxidants reacting to form a stable product
• Metal ion chelation
• Immediate termination of the chain

Correct Answer: Drug radical reacting with oxygen to form peroxy radical

Q5. Termination of a radical chain reaction is achieved by which process?

• Regeneration of radicals
• Recombination of two radicals to form a stable, non-radical product
• Ionization of the drug molecule
• Increase in dissolved oxygen

Correct Answer: Recombination of two radicals to form a stable, non-radical product

Q6. Which common metal ions catalyze oxidative degradation in pharmaceutical formulations?

• Sodium and potassium
• Calcium and magnesium
• Iron (Fe2+/Fe3+) and copper (Cu+/Cu2+)
• Zinc and manganese only

Correct Answer: Iron (Fe2+/Fe3+) and copper (Cu+/Cu2+)

Q7. Which additive is most appropriate for binding trace metal ions to reduce catalyzed oxidation?

• BHT (butylated hydroxytoluene)
• EDTA (ethylenediaminetetraacetic acid)
• Ascorbic acid
• Tocopherol

Correct Answer: EDTA (ethylenediaminetetraacetic acid)

Q8. Which class of antioxidants primarily acts as radical chain terminators by donating a hydrogen atom?

• Primary (chain-breaking) antioxidants
• Secondary (peroxide-decomposing) antioxidants
• Chelating agents
• Buffering agents

Correct Answer: Primary (chain-breaking) antioxidants

Q9. Which of the following is a common primary (chain-breaking) antioxidant used in formulations?

• BHT (butylated hydroxytoluene)
• EDTA
• Sodium chloride
• Magnesium stearate

Correct Answer: BHT (butylated hydroxytoluene)

Q10. Which antioxidant is primarily a reducing agent that can act sacrificially to protect drug molecules?

• Tocopherol (vitamin E)
• Ascorbic acid (vitamin C)
• BHA (butylated hydroxyanisole)
• Polysorbate 80

Correct Answer: Ascorbic acid (vitamin C)

Q11. Which excipient is notorious for forming hydroperoxides that can oxidize drugs?

• Microcrystalline cellulose
• Polysorbates (Tweens)
• Silicon dioxide
• Magnesium oxide

Correct Answer: Polysorbates (Tweens)

Q12. What analytical test is commonly used to detect hydroperoxides or peroxide value in a sample?

• pH titration
• Iodometric titration (peroxide value) using KI
• Karl Fischer titration
• UV absorbance at 260 nm only

Correct Answer: Iodometric titration (peroxide value) using KI

Q13. Photoxidation often proceeds via which reactive species generated by a photosensitizer?

• Singlet oxygen (1O2)
• Nitrogen gas
• Carbon dioxide radical anion
• Hydrogen gas

Correct Answer: Singlet oxygen (1O2)

Q14. Which formulation strategy is effective at reducing oxidation by minimizing dissolved oxygen?

• Nitrogen or argon purging (inert-gas blanketing)
• Increasing headspace oxygen
• Storing at high humidity
• Adding more water to formulations

Correct Answer: Nitrogen or argon purging (inert-gas blanketing)

Q15. Which packaging choice best reduces both oxygen ingress and light-induced oxidation?

• Clear PET bottle with large headspace
• Amber glass vial with oxygen-impermeable closure
• Paperboard box without inner bag
• Perforated plastic film

Correct Answer: Amber glass vial with oxygen-impermeable closure

Q16. How does pH generally influence oxidative degradation of ionizable drugs?

• pH has no effect on oxidation
• Only extremely acidic pH prevents oxidation
• pH affects drug ionization and reactive site availability, altering oxidation rate
• Alkaline conditions always eliminate oxidation

Correct Answer: pH affects drug ionization and reactive site availability, altering oxidation rate

Q17. Which antioxidant class decomposes hydroperoxides and thereby prevents propagation?

• Primary antioxidants
• Secondary antioxidants (peroxide decomposers like phosphites)
• Buffering agents
• Antifoaming agents

Correct Answer: Secondary antioxidants (peroxide decomposers like phosphites)

Q18. Which commonly used antioxidant in topical and oral formulations is a natural chain-breaking antioxidant?

• Sodium benzoate
• Alpha-tocopherol (vitamin E)
• Sodium chloride
• Calcium carbonate

Correct Answer: Alpha-tocopherol (vitamin E)

Q19. What potential adverse effect can high concentrations of certain antioxidants (e.g., ascorbate) have in formulations?

• They become inert and ineffective
• They may act as pro-oxidants under some conditions
• They always increase viscosity
• They neutralize buffers completely

Correct Answer: They may act as pro-oxidants under some conditions

Q20. The Fenton reaction is important in metal-catalyzed oxidation. Which equation represents the classic Fenton reaction?

• Fe2+ + H2O2 → Fe3+ + OH• + OH−
• Fe3+ + H2O2 → Fe2+ + O2
• Cu2+ + O2 → Cu+ + O2•−
• Zn2+ + H2O → ZnOH+

Correct Answer: Fe2+ + H2O2 → Fe3+ + OH• + OH−

Q21. Which of the following is a common strategy to stabilize oxidation-sensitive drugs during freeze-drying?

• Increase headspace oxygen before lyophilization
• Add protective excipients (sugars, bulking agents) and perform under inert atmosphere
• Expose to light to drive off oxygen
• Use metal containers without chelators

Correct Answer: Add protective excipients (sugars, bulking agents) and perform under inert atmosphere

Q22. Which surfactant often requires antioxidant control because it can form peroxides during storage?

• Sodium lauryl sulfate
• Polysorbate 20 or 80 (Tweens)
• Hydroxypropyl methylcellulose
• Carbomers

Correct Answer: Polysorbate 20 or 80 (Tweens)

Q23. Which analytical indicator is most useful for monitoring early oxidative degradation in lipid-containing formulations?

• Peroxide value measurement
• Residual solvent analysis
• Microbial limit test
• Melting point determination

Correct Answer: Peroxide value measurement

Q24. According to Arrhenius behavior, how does temperature affect the rate constant (k) of oxidation?

• k decreases exponentially with increasing temperature
• k remains constant regardless of temperature
• k increases exponentially with increasing temperature
• k changes linearly and unpredictably with temperature

Correct Answer: k increases exponentially with increasing temperature

Q25. Which antioxidant is commonly used in parenteral products but can cause hypersensitivity in some patients?

• Sodium metabisulfite
• BHT
• EDTA
• Magnesium sulfate

Correct Answer: Sodium metabisulfite

Q26. What is the role of oxygen scavengers incorporated into packaging?

• To increase headspace oxygen
• To chemically remove residual oxygen and extend shelf life
• To add moisture to the package
• To catalyze oxidation intentionally

Correct Answer: To chemically remove residual oxygen and extend shelf life

Q27. Which formulation excipient is known to accelerate oxidation via trace peroxide formation and requires careful control?

• Polyethylene glycol (PEG)
• Microcrystalline cellulose
• Calcium phosphate
• Talc

Correct Answer: Polyethylene glycol (PEG)

Q28. Which regulatory guideline specifically outlines stability testing for new drug substances and products?

• ICH Q1A(R2)
• USP <741>
• FDA Guidance on Carcinogens
• EMA GMP Annex 1

Correct Answer: ICH Q1A(R2)

Q29. For an oxidation-prone drug, which combination of strategies is most comprehensive for stabilization?

• Expose to light, increase temperature, add metal ions
• Use antioxidants, chelators, inert-gas blanketing, and protective packaging
• Remove antioxidants and increase headspace oxygen
• Store at high humidity with permeable packaging

Correct Answer: Use antioxidants, chelators, inert-gas blanketing, and protective packaging

Q30. Which analytical approach helps distinguish between photodegradation and autoxidation pathways during stability studies?

• Comparing samples stored in light vs protected from light under identical oxygen and temperature conditions
• Only measuring pH changes
• Measuring viscosity changes alone
• Monitoring microbial growth

Correct Answer: Comparing samples stored in light vs protected from light under identical oxygen and temperature conditions