Temperature effect on drug stability MCQs With Answer

Understanding how temperature affects drug stability is essential for B.Pharm students involved in formulation, quality control, and regulatory affairs. Temperature influences degradation kinetics, hydrolysis, oxidation, polymorphic transitions, and denaturation of biologics, all of which determine shelf-life and required storage conditions. Core concepts include the Arrhenius equation, activation energy, Q10 rule, ICH stability protocols, and cold chain management. Practical understanding of temperature-driven pH shifts, solubility changes, and packaging interactions helps design stability studies and mitigation strategies such as refrigeration, lyophilization, and protective excipients. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary effect of increasing temperature on drug chemical stability?

• It decreases molecular motion and slows degradation
• It increases molecular motion and accelerates chemical degradation rates
• It always converts drugs into more stable polymorphs
• It neutralizes impurities and prevents degradation

Correct Answer: It increases molecular motion and accelerates chemical degradation rates

Q2. Which equation quantitatively relates the rate constant of a degradation reaction to temperature?

• Van’t Hoff equation
• Henderson–Hasselbalch equation
• Arrhenius equation
• Michaelis–Menten equation

Correct Answer: Arrhenius equation

Q3. Which kinetic order is most commonly observed for many drug degradation reactions in solution?

• Zero-order kinetics
• First-order kinetics
• Second-order kinetics
• Fractional-order kinetics

Correct Answer: First-order kinetics

Q4. What does the Q10 value represent in stability studies?

• The activation energy divided by 10
• The factor by which reaction rate changes for a 10°C temperature change
• The percent loss after 10 days at accelerated conditions
• The temperature at which 10% degradation occurs

Correct Answer: The factor by which reaction rate changes for a 10°C temperature change

Q5. According to ICH guidelines, which accelerated stability condition is commonly used for solid oral products?

• 25°C / 40% RH
• 30°C / 65% RH
• 40°C / 75% RH
• 5°C / 60% RH

Correct Answer: 40°C / 75% RH

Q6. What temperature range defines standard refrigerated storage for many pharmaceuticals?

• -20°C to -10°C
• 0°C to 2°C
• 2°C to 8°C
• 15°C to 25°C

Correct Answer: 2°C to 8°C

Q7. How can freezing negatively affect the stability of a drug product, especially biologics?

• Freezing always stabilizes drugs by stopping all reactions
• Ice formation concentrates solutes, causing pH shifts and protein denaturation
• Freezing converts all polymorphs to a single stable form
• Freezing increases water activity and accelerates hydrolysis

Correct Answer: Ice formation concentrates solutes, causing pH shifts and protein denaturation

Q8. Which thermal analytical technique is commonly used to determine melting points and thermal transitions related to stability?

• High-performance liquid chromatography (HPLC)
• Differential scanning calorimetry (DSC)
• Mass spectrometry (MS)
• Ultraviolet-visible spectroscopy (UV-Vis)

Correct Answer: Differential scanning calorimetry (DSC)

Q9. In what units is activation energy (Ea) typically reported in pharmaceutical stability studies?

• kJ/mol
• mol/kJ
• seconds
• grams

Correct Answer: kJ/mol

Q10. On an Arrhenius plot of ln(k) versus 1/T, the slope equals:

• +Ea / R
• -Ea / R
• R / Ea
• Zero

Correct Answer: -Ea / R

Q11. Which situation is a common reason why Arrhenius extrapolation may give misleading shelf-life predictions?

• The drug’s concentration is too high
• The degradation mechanism changes at different temperatures
• Analytical methods are too sensitive
• Storage containers are impermeable

Correct Answer: The degradation mechanism changes at different temperatures

Q12. Which degradation pathway is most directly influenced by both temperature and humidity?

• Photolysis
• Hydrolysis
• Radioactive decay
• None—humidity does not affect degradation

Correct Answer: Hydrolysis

Q13. For protein therapeutics, the primary effect of elevated temperature is:

• Increased solubility without structural change
• Protein unfolding and aggregation (denaturation)
• Formation of new covalent small molecules
• Complete chemical inertness

Correct Answer: Protein unfolding and aggregation (denaturation)

Q14. What does t90 refer to in stability terminology?

• Time to reach 90% degradation
• Time during which 90% of drug remains (10% loss)
• Temperature at which 90% solubility occurs
• Tenfold increase in degradation rate

Correct Answer: Time during which 90% of drug remains (10% loss)

Q15. Which packaging strategy best helps prevent temperature-related degradation during transport?

• Glass vials with no insulation
• Insulated containers with validated cold packs and data loggers
• Opaque cardboard boxes only
• Loose-packed frozen gel packs without monitoring

Correct Answer: Insulated containers with validated cold packs and data loggers

Q16. Repeated temperature cycling (freeze-thaw or warm-cool cycles) most commonly causes:

• Improved chemical stability
• Physical instability such as precipitation, crystallization, or phase separation
• Permanent sterilization
• Complete protection from oxidation

Correct Answer: Physical instability such as precipitation, crystallization, or phase separation

Q17. Which approach is typically used to estimate shelf-life from short-term elevated temperature data?

• Extrapolation using Arrhenius kinetics from accelerated stability studies
• Direct measurement at only one high temperature
• Ignoring temperature and using ambient samples
• Estimating by container color

Correct Answer: Extrapolation using Arrhenius kinetics from accelerated stability studies

Q18. Which factor is not directly accounted for by a simple Arrhenius model?

• Temperature dependence of the rate constant
• Activation energy magnitude
• Change in degradation pathway at different temperatures
• Boltzmann distribution of molecular energies

Correct Answer: Change in degradation pathway at different temperatures

Q19. Elevated temperature can induce polymorphic conversion. Which outcome is most likely if a drug converts to a more stable polymorph?

• Increased solubility and immediate dissolution
• Reduced solubility and altered bioavailability
• Spontaneous sterilization of the product
• No change to any pharmaceutical property

Correct Answer: Reduced solubility and altered bioavailability

Q20. For many routine vaccines, which storage condition maintains potency during distribution?

• Room temperature (25–30°C)
• Frozen (< -20°C)
• Refrigerated (2–8°C)
• Exposed to sunlight

Correct Answer: Refrigerated (2–8°C)

Q21. Which device is most appropriate to document temperature conditions during shipment?

• pH meter
• Temperature data logger
• UV lamp
• Analytical balance

Correct Answer: Temperature data logger

Q22. ICH defines “controlled room temperature” for stability purposes as approximately which range?

• -5°C to 5°C
• 8°C to 15°C
• 20°C to 25°C
• 30°C to 40°C

Correct Answer: 20°C to 25°C

Q23. If a drug has a Q10 value of 2, how does the reaction rate at 30°C compare to 20°C?

• It is half the rate at 20°C
• It is twice the rate at 20°C
• It is unchanged
• It is ten times the rate at 20°C

Correct Answer: It is twice the rate at 20°C

Q24. How does lyophilization (freeze-drying) improve stability of sensitive drug products?

• By increasing the water content to prevent crystallization
• By removing water to reduce hydrolysis and slow degradation
• By raising the storage temperature requirement
• By converting the drug into a gaseous form

Correct Answer: By removing water to reduce hydrolysis and slow degradation

Q25. For most solid drug substances, how does solubility in a solvent change with increasing temperature?

• Solubility typically decreases
• Solubility typically increases
• Solubility remains exactly the same
• Solubility becomes zero

Correct Answer: Solubility typically increases

Q26. What is a temperature excursion in the context of pharmaceutical storage?

• A planned increase in potency
• A temporary deviation from recommended storage temperatures
• Permanent conversion to another polymorph
• A type of microbial contamination

Correct Answer: A temporary deviation from recommended storage temperatures

Q27. Which parameter is most commonly used to set an expiry date for a drug product under labeled storage conditions?

• Tmax (time to maximum concentration)
• t90 or the time to 90% remaining potency
• Melting point
• Particle size distribution

Correct Answer: t90 or the time to 90% remaining potency

Q28. Which spectroscopic method is commonly used to monitor temperature-induced changes in protein secondary structure?

• Gas chromatography (GC)
• Polarimetry
• Circular dichroism (CD) spectroscopy
• Flame photometry

Correct Answer: Circular dichroism (CD) spectroscopy

Q29. How can temperature changes influence the pH of a buffered formulation?

• Temperature has no effect on pH
• Temperature can shift pKa values, causing pH changes that affect stability
• Temperature always neutralizes the buffer
• Buffers become toxic at higher temperature

Correct Answer: Temperature can shift pKa values, causing pH changes that affect stability

Q30. Which statement best describes a limitation of accelerated stability testing using high temperatures?

• Accelerated testing always perfectly predicts real-time shelf-life
• High-temperature testing can change the degradation pathway, making extrapolation unreliable
• Accelerated testing is unnecessary for regulatory submissions
• High temperatures never affect physical properties

Correct Answer: High-temperature testing can change the degradation pathway, making extrapolation unreliable