Hydrolysis – stabilization of drugs MCQs With Answer

Hydrolysis – stabilization of drugs is a key topic in pharmaceutical stability that examines how water and chemical conditions break down drug molecules and how formulators prevent this degradation. This introduction covers hydrolytic pathways (acid-, base- and water-catalyzed), susceptible functional groups (esters, amides, lactones, carbamates, β‑lactams, glycosides), influential factors (pH, temperature, solvent, moisture, metal ions) and practical stabilization strategies (pH control, buffers, co‑solvents, lyophilization, complexation, chelators, protective coatings and packaging). Understanding kinetics, formulation choices and analytical monitoring is essential for extending shelf‑life and ensuring safety and efficacy. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which functional group is most commonly prone to rapid hydrolysis in aqueous formulations?

• Ester
• Ether
• Arene
• Thioether

Correct Answer: Ester

Q2. Acid-catalyzed hydrolysis is favored when the drug solution has which characteristic?

• High pH (alkaline)
• Low pH (acidic)
• Neutral pH
• High ionic strength only

Correct Answer: Low pH (acidic)

Q3. Base-catalyzed hydrolysis typically proceeds by which mechanistic step?

• Nucleophilic attack by hydroxide on the electrophilic carbonyl
• Protonation of the leaving group
• Radical abstraction of hydrogen
• Oxidative cleavage by molecular oxygen

Correct Answer: Nucleophilic attack by hydroxide on the electrophilic carbonyl

Q4. Which kinetic order often describes hydrolysis of a drug in large excess of water?

• Zero order
• First order (pseudo-first-order)
• Second order
• Mixed order only

Correct Answer: First order (pseudo-first-order)

Q5. Which formulation approach reduces hydrolysis by removing water?

• Lyophilization (freeze-drying)
• Adding a chelating agent
• Using glass vials
• Increasing buffer concentration

Correct Answer: Lyophilization (freeze-drying)

Q6. Which excipient can complex metal ions that catalyze hydrolysis?

• EDTA
• Sucrose
• Polysorbate 80
• Mannitol

Correct Answer: EDTA

Q7. Cyclodextrin complexation primarily stabilizes drugs by what mechanism?

• Lowering solution pH
• Sequestering the drug from bulk water
• Acting as an antioxidant
• Increasing ionic strength

Correct Answer: Sequestering the drug from bulk water

Q8. Which drug is a classic example of ester hydrolysis in aqueous media?

• Aspirin (acetylsalicylic acid)
• Metformin
• Penicillin V
• Insulin

Correct Answer: Aspirin (acetylsalicylic acid)

Q9. For pH-rate profiling, what does a V-shaped pH-rate profile typically indicate?

• Only acid catalysis
• Both acid and base catalysis with a minimum rate near neutrality
• No pH dependence
• Only base catalysis

Correct Answer: Both acid and base catalysis with a minimum rate near neutrality

Q10. Which packaging property most directly reduces hydrolysis for moisture-sensitive drugs?

• Light protection
• Low oxygen permeability
• Low water vapor transmission rate (WVTR)
• Metallic color

Correct Answer: Low water vapor transmission rate (WVTR)

Q11. Which solvent modification can slow hydrolysis by reducing water activity?

• Adding co‑solvents like ethanol or PEG
• Adding extra water
• Removing buffer salts
• Lowering drug concentration only

Correct Answer: Adding co‑solvents like ethanol or PEG

Q12. Metal ion catalysis accelerates hydrolysis primarily by:

• Increasing solution temperature
• Coordinating and activating carbonyl groups toward nucleophilic attack
• Reducing pH drastically
• Acting as antioxidants

Correct Answer: Coordinating and activating carbonyl groups toward nucleophilic attack

Q13. Which of the following is NOT an effective strategy to stabilize a hydrolytically labile drug?

• Formulate as a dry powder for reconstitution
• Use buffer at optimal pH
• Increase storage temperature intentionally
• Incorporate stabilizing excipients

Correct Answer: Increase storage temperature intentionally

Q14. The Arrhenius equation is used in stability studies to:

• Determine buffer composition
• Estimate temperature dependence of degradation rate and predict shelf-life
• Measure water activity directly
• Calculate pH of the solution

Correct Answer: Estimate temperature dependence of degradation rate and predict shelf-life

Q15. Which analytical method is considered stability-indicating for monitoring hydrolysis?

• UV-visible spectroscopy without separation
• Stability-indicating HPLC with suitable detection
• Titration only
• Simple visual inspection

Correct Answer: Stability-indicating HPLC with suitable detection

Q16. Prodrug design to prevent hydrolysis often involves:

• Converting a susceptible group to a more stable promoiety that is metabolized in vivo
• Removing all polar groups
• Adding heavy metals
• Freezing the formulation

Correct Answer: Converting a susceptible group to a more stable promoiety that is metabolized in vivo

Q17. Which of the following functional groups is generally more resistant to hydrolysis?

• Amide (secondary amide)
• Ester
• Anhydride
• Acyl chloride

Correct Answer: Amide (secondary amide)

Q18. Moisture sorption by hygroscopic excipients can increase hydrolysis risk by:

• Decreasing the amount of dissolved drug
• Raising local water activity and facilitating hydrolytic reaction
• Lowering pH to extreme alkalinity
• Preventing microbial growth

Correct Answer: Raising local water activity and facilitating hydrolytic reaction

Q19. Which buffer characteristic is important to minimize catalyzed hydrolysis?

• High buffer capacity at the chosen optimum pH
• Buffer with strong oxidizing properties
• Buffer that increases ionic strength only
• Buffer with high surfactant activity

Correct Answer: High buffer capacity at the chosen optimum pH

Q20. Beta-lactam antibiotics hydrolyze primarily through attack on which bond?

• The beta-lactam amide bond
• Aromatic C–H bond
• Ether linkage
• Sulfide bond

Correct Answer: The beta-lactam amide bond

Q21. Which process can protect oral solid dosage forms from gastric hydrolysis?

• Immediate-release film coating
• Enteric coating that delays release until higher intestinal pH
• Adding more disintegrant
• Compressing at very low pressure only

Correct Answer: Enteric coating that delays release until higher intestinal pH

Q22. Temperature increases typically have what effect on hydrolysis rate?

• Decrease rate
• No effect
• Increase rate exponentially according to activation energy
• Cause racemization only

Correct Answer: Increase rate exponentially according to activation energy

Q23. Which excipient class can sometimes accelerate hydrolysis by providing catalytic microenvironments?

• Bulking agents like mannitol
• Surfactants such as polysorbates
• Non-reactive fillers like microcrystalline cellulose
• Inert glass beads

Correct Answer: Surfactants such as polysorbates

Q24. In a pseudo-first-order hydrolysis experiment, which parameter is typically kept in large excess?

• Drug concentration
• Catalyst concentration
• Water concentration
• Buffer concentration always

Correct Answer: Water concentration

Q25. Which stabilization technique protects sensitive drugs by physical isolation from water?

• Co-crystallization with water-soluble partners
• Microencapsulation or encapsulation in oil-based systems
• Adding hydrophilic polymers to solution
• Reducing drug dose

Correct Answer: Microencapsulation or encapsulation in oil-based systems

Q26. Which parameter is least relevant when designing accelerated stability studies for hydrolysis?

• Storage temperature
• Relative humidity
• Light exposure if photolabile
• Patient adherence

Correct Answer: Patient adherence

Q27. Which additive is used to stabilize proteins against hydrolytic fragmentation?

• Proteases
• Sugars like trehalose or sucrose as stabilizers
• Sodium dodecyl sulfate
• EDTA only

Correct Answer: Sugars like trehalose or sucrose as stabilizers

Q28. Which statement about water activity (aw) and hydrolysis is correct?

• Lower aw always increases hydrolysis
• Higher aw generally increases the rate of hydrolysis
• aw has no relation to hydrolysis
• Only relative humidity matters, not aw

Correct Answer: Higher aw generally increases the rate of hydrolysis

Q29. Which manufacturing control reduces hydrolysis during wet granulation?

• Allowing high moisture and long wet time
• Optimizing granulation time and minimizing water, or using non-aqueous granulation
• Using metal contact surfaces exclusively
• Skipping drying steps

Correct Answer: Optimizing granulation time and minimizing water, or using non-aqueous granulation

Q30. Which is a common indicator that a drug has undergone hydrolysis during stability testing?

• Formation of new peaks corresponding to hydrolytic products in HPLC
• Increase in tablet hardness only
• Unchanged chromatogram over time
• Improved solubility without degradation products

Correct Answer: Formation of new peaks corresponding to hydrolytic products in HPLC