Preparation and stability of buffers MCQs With Answer

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Preparation and stability of buffers MCQs with answers will help B. Pharm students master essential concepts in pharmaceutical buffer systems. This topic covers buffer selection, Henderson–Hasselbalch equation, buffer capacity, ionic strength, temperature effects, CO2 absorption, sterilization, preservatives, and compatibility with drugs and containers. You’ll learn how to prepare acetate, phosphate, citrate, borate, and Good’s buffers; optimize pH and buffer capacity; minimize pH drift; and ensure stability in parenteral, ophthalmic, and oral formulations. Key keywords: buffer preparation, buffer stability, buffer capacity, Henderson–Hasselbalch, pharmaceutical buffers, pH control, isotonicity, Good’s buffers, sterilization, CO2 uptake, ionic strength. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the primary purpose of using buffers in pharmaceutical formulations?

  • To maintain the pH within a narrow range to ensure drug stability and performance
  • To increase the solubility of all drugs regardless of their properties
  • To act as a preservative against microbial growth
  • To improve organoleptic properties only

Correct Answer: To maintain the pH within a narrow range to ensure drug stability and performance

Q2. The best criterion for selecting a buffer pair for a target pH is:

  • Choose a buffer whose pKa is within ±1 pH unit of the target pH
  • Choose the buffer with the highest molecular weight
  • Choose the buffer with the lowest cost only
  • Choose a strong acid and its neutral salt

Correct Answer: Choose a buffer whose pKa is within ±1 pH unit of the target pH

Q3. The Henderson–Hasselbalch equation for an acid buffer is:

  • pH = pKa + log10([A−]/[HA])
  • pH = pKa − log10([A−]/[HA])
  • pH = pKb + log10([B]/[BH+])
  • pOH = pKa + log10([A−]/[HA])

Correct Answer: pH = pKa + log10([A−]/[HA])

Q4. For an acetate buffer (pKa = 4.76) targeting pH 5.00, the required [A−]/[HA] ratio is approximately:

  • 1.74
  • 0.57
  • 10.0
  • 0.10

Correct Answer: 1.74

Q5. Buffer capacity generally increases with:

  • Higher total molar concentration of the conjugate acid–base pair
  • Lower ionic strength of the solution
  • Using strong acids and bases instead of weak pairs
  • Decreasing the ratio [base]/[acid]

Correct Answer: Higher total molar concentration of the conjugate acid–base pair

Q6. Maximum buffer capacity for a weak acid buffer occurs when:

  • [A−] = [HA]
  • [A−] ≫ [HA]
  • [A−] ≪ [HA]
  • [A−]/[HA] = 10

Correct Answer: [A−] = [HA]

Q7. Upon dilution of a buffer while maintaining the same [A−]/[HA] ratio, the most likely outcome is:

  • Buffer capacity decreases; pH changes only slightly
  • Buffer capacity increases; pH remains constant
  • Both pH and buffer capacity increase significantly
  • Both pH and buffer capacity remain exactly unchanged

Correct Answer: Buffer capacity decreases; pH changes only slightly

Q8. Which combination will form an effective buffer?

  • Weak acid and its conjugate base (salt)
  • Strong acid and its neutral salt
  • Strong base and its neutral salt
  • Neutral salt and water

Correct Answer: Weak acid and its conjugate base (salt)

Q9. Which of the following is NOT a buffer system?

  • HCl and NaCl
  • Acetic acid and sodium acetate
  • Ammonia and ammonium chloride
  • Monobasic and dibasic sodium phosphate

Correct Answer: HCl and NaCl

Q10. The most suitable buffer pair for formulations at pH ~7.4 is typically:

  • Dihydrogen phosphate/hydrogen phosphate
  • Acetic acid/acetate
  • Borate/boric acid
  • Carbonic acid/bicarbonate without CO2 control

Correct Answer: Dihydrogen phosphate/hydrogen phosphate

Q11. For a phosphate buffer (pKa2 = 7.21), the [base]/[acid] ratio needed for pH 7.40 is about:

  • 1.55
  • 0.64
  • 3.16
  • 0.10

Correct Answer: 1.55

Q12. Which statement about TRIS buffers is true?

  • pH decreases with increasing temperature (about −0.028 pH/°C)
  • pH increases with increasing temperature for TRIS
  • TRIS pH is temperature independent
  • TRIS cannot form buffers near neutral pH

Correct Answer: pH decreases with increasing temperature (about −0.028 pH/°C)

Q13. Why should pH be measured at the temperature of use?

  • Because dissociation constants and electrode responses are temperature dependent
  • Because buffers evaporate only at high temperatures
  • Because ionic strength is independent of temperature
  • Because color indicators are not temperature sensitive

Correct Answer: Because dissociation constants and electrode responses are temperature dependent

Q14. Which buffer should be avoided in calcium-containing parenterals due to precipitation risk?

  • Phosphate buffer
  • Citrate buffer
  • Acetate buffer
  • Histidine buffer

Correct Answer: Phosphate buffer

Q15. Which buffer is generally avoided for systemic formulations in infants due to toxicity concerns?

  • Borate buffer
  • Phosphate buffer
  • Acetate buffer
  • Citrate buffer

Correct Answer: Borate buffer

Q16. The tear fluid is most comfortable at approximately:

  • pH 7.4
  • pH 5.0
  • pH 9.5
  • pH 3.0

Correct Answer: pH 7.4

Q17. For ophthalmic solutions, buffer capacity should generally be:

  • Low, to allow tears to rapidly adjust the pH
  • Very high, to resist any tear dilution
  • Zero, to avoid any ions
  • Irrelevant, only tonicity matters

Correct Answer: Low, to allow tears to rapidly adjust the pH

Q18. Which method is commonly used to adjust tonicity in buffered formulations?

  • Sodium chloride equivalent (E-value) method
  • Tyndall effect method
  • Partition coefficient method
  • Molar refraction method

Correct Answer: Sodium chloride equivalent (E-value) method

Q19. For acetic acid/acetate buffer (pKa = 4.76) targeting pH 4.50, the [A−]/[HA] ratio is approximately:

  • 0.55
  • 1.82
  • 3.16
  • 10.0

Correct Answer: 0.55

Q20. A desirable feature of Good’s buffers (e.g., HEPES, MOPS) is:

  • Minimal metal binding and low temperature/ionic strength dependence
  • High UV absorbance to monitor easily
  • Strong chelation that inactivates enzymes
  • High volatility

Correct Answer: Minimal metal binding and low temperature/ionic strength dependence

Q21. Which statement about CO2 and buffers is correct?

  • Absorption of CO2 lowers the pH of alkaline buffers over time
  • Absorption of CO2 raises the pH of alkaline buffers
  • CO2 has no effect on pH
  • CO2 only affects acidic buffers

Correct Answer: Absorption of CO2 lowers the pH of alkaline buffers over time

Q22. To minimize CO2 uptake during storage, buffers should be:

  • Stored in tightly closed containers with minimal headspace
  • Stored open to the air to equilibrate
  • Stored at high temperature
  • Continuously stirred

Correct Answer: Stored in tightly closed containers with minimal headspace

Q23. Which preservative’s effectiveness is greatly reduced at higher pH due to ionization?

  • Benzoic acid/benzoate
  • Benzalkonium chloride
  • Phenol
  • Chlorobutanol

Correct Answer: Benzoic acid/benzoate

Q24. An example of an alkaline buffer system is:

  • Ammonia/ammonium chloride
  • Acetic acid/sodium acetate
  • Citrate/citric acid
  • Carbonic acid/bicarbonate (open to air)

Correct Answer: Ammonia/ammonium chloride

Q25. Buffer capacity is maximized at which condition for a weak acid buffer?

  • pH = pKa
  • pH = pKa + 2
  • pH = pKa − 2
  • Any pH, capacity is constant

Correct Answer: pH = pKa

Q26. Excessive dilution of a buffer in a dosage form primarily risks:

  • Increased pH drift leading to drug instability
  • Immediate precipitation of all solutes
  • Complete loss of isotonicity
  • Excessive viscosity

Correct Answer: Increased pH drift leading to drug instability

Q27. Ionic strength in buffer solutions is important because it:

  • Affects activity coefficients and thus the effective pH
  • Determines color intensity
  • Eliminates the need for preservatives
  • Prevents evaporation

Correct Answer: Affects activity coefficients and thus the effective pH

Q28. The first step in buffer preparation for a target pH should be to:

  • Select a conjugate acid–base pair with pKa near the target pH
  • Add strong acid to reach the pH and then choose a buffer
  • Autoclave the solution before choosing components
  • Adjust tonicity before selecting the buffer system

Correct Answer: Select a conjugate acid–base pair with pKa near the target pH

Q29. Which buffer is a Good’s buffer suitable for biological systems near neutral pH?

  • HEPES
  • Borate
  • Carbonate
  • Tartrate

Correct Answer: HEPES

Q30. Citrate buffers often help stabilize formulations by:

  • Chelating trace metals that catalyze oxidation
  • Providing strong alkalinity above pH 10
  • Eliminating the need for antioxidants
  • Increasing microbial growth

Correct Answer: Chelating trace metals that catalyze oxidation

Q31. Buffer control can improve drug stability primarily by reducing:

  • Specific acid or base catalyzed degradation rates
  • Osmotic pressure
  • Surface tension
  • Boiling point

Correct Answer: Specific acid or base catalyzed degradation rates

Q32. A buffer commonly used for protein formulations around pH 6.0 is:

  • Histidine buffer
  • Borate buffer
  • Sodium hydroxide/NaCl
  • Sodium carbonate/bicarbonate

Correct Answer: Histidine buffer

Q33. When preparing a buffer with a weak base and its salt, the Henderson–Hasselbalch equation is best applied using:

  • The pKa of the conjugate acid and the ratio [base]/[acid]
  • The pKb of the base and the ratio [acid]/[base]
  • The pKw directly without any pKa or pKb
  • No equilibrium constants are needed

Correct Answer: The pKa of the conjugate acid and the ratio [base]/[acid]

Q34. For ammonium buffer (pKa of NH4+ = 9.25) targeting pH 9.75, the [base]/[acid] ratio is approximately:

  • 3.16
  • 1.00
  • 0.32
  • 10.00

Correct Answer: 3.16

Q35. Adding a small amount of strong acid to an unbuffered solution compared to a buffered solution will cause:

  • A much larger pH change in the unbuffered solution
  • An identical pH change in both
  • No pH change in the unbuffered solution
  • No pH change in the buffered solution

Correct Answer: A much larger pH change in the unbuffered solution

Q36. Buffer capacity is defined as the:

  • Amount of strong acid/base (in equivalents per liter) needed to change pH by one unit
  • Concentration of the buffer components
  • Volume of buffer needed to dissolve a drug
  • Osmolarity of the buffer

Correct Answer: Amount of strong acid/base (in equivalents per liter) needed to change pH by one unit

Q37. Which water is preferred when preparing alkaline buffers to minimize initial CO2 content?

  • Freshly boiled and cooled, CO2-free water
  • Carbonated water
  • Tap water exposed to air overnight
  • Distilled water stored uncapped

Correct Answer: Freshly boiled and cooled, CO2-free water

Q38. The practical buffering range for acetate buffer (pKa 4.76) is approximately:

  • pH 3.8–5.8
  • pH 6.5–8.5
  • pH 8.5–10.5
  • pH 1.0–3.0

Correct Answer: pH 3.8–5.8

Q39. The pKa values for phosphoric acid relevant to buffer preparation include:

  • Approximately 2.15, 7.21, and 12.3
  • Approximately 3.0, 6.0, and 9.0
  • Approximately 1.0, 5.0, and 11.0
  • Only a single pKa around 7.0

Correct Answer: Approximately 2.15, 7.21, and 12.3

Q40. Mixing 100 mL of 0.1 M acetic acid with 100 mL of 0.1 M sodium acetate yields a pH approximately equal to:

  • 4.76
  • 1.00
  • 7.00
  • 9.25

Correct Answer: 4.76

Q41. Doubling both acid and base concentrations in a buffer while keeping their ratio constant will:

  • Keep pH the same but increase buffer capacity
  • Increase pH and decrease buffer capacity
  • Decrease pH and increase buffer capacity
  • Keep both pH and buffer capacity unchanged

Correct Answer: Keep pH the same but increase buffer capacity

Q42. A suitable sterilization method for heat-labile buffered solutions is:

  • Membrane filtration through 0.22 μm filters
  • Autoclaving at 134°C for 30 minutes
  • Dry heat sterilization at 160°C
  • Gamma irradiation by default

Correct Answer: Membrane filtration through 0.22 μm filters

Q43. Borate buffers are typically used in which pH range and have which limitation?

  • pH 8–10; unsuitable for systemic and pediatric use
  • pH 3–5; unstable at room temperature
  • pH 5–7; precipitate with calcium
  • pH 1–3; highly compatible parenterally

Correct Answer: pH 8–10; unsuitable for systemic and pediatric use

Q44. The carbonate/bicarbonate buffer (pKa2 ≈ 10.33) is most effective around:

  • pH 9.3–11.3
  • pH 4.3–6.3
  • pH 6.8–8.8
  • pH 2.0–4.0

Correct Answer: pH 9.3–11.3

Q45. A general rule for effective buffering is that it occurs within:

  • ±1 pH unit of the buffer’s pKa
  • ±3 pH units of the buffer’s pKa
  • Any pH, no relation to pKa
  • Only at pH 7.0

Correct Answer: ±1 pH unit of the buffer’s pKa

Q46. To minimize pH drift of alkaline buffers during storage, one should:

  • Fill containers fully and use tight closures to minimize headspace
  • Use vented caps to allow gas exchange
  • Store with desiccant only
  • Use rubber stoppers with high gas permeability

Correct Answer: Fill containers fully and use tight closures to minimize headspace

Q47. During buffer preparation, pH adjustment should be done:

  • After the solution has equilibrated to the measurement temperature
  • Immediately after dissolving salts, regardless of temperature
  • Before dissolving the buffer components
  • Only after sterilization

Correct Answer: After the solution has equilibrated to the measurement temperature

Q48. For any buffer system, when pH equals pKa, the ratio [base]/[acid] equals:

  • 1
  • 0.1
  • 10
  • 0.01

Correct Answer: 1

Q49. In preparing a phosphate buffer at pH 6.8, which component should predominate?

  • Monobasic phosphate (H2PO4−) over dibasic (HPO4^2−)
  • Dibasic phosphate (HPO4^2−) over monobasic (H2PO4−)
  • Tribasic phosphate (PO4^3−) only
  • Phosphoric acid only

Correct Answer: Monobasic phosphate (H2PO4−) over dibasic (HPO4^2−)

Q50. Which statement best guides buffer concentration selection for stability?

  • Use the lowest concentration that maintains pH control to avoid catalysis of degradation
  • Use the highest concentration possible for maximum resistance
  • Concentration does not affect degradation
  • Buffers always inhibit hydrolysis regardless of concentration

Correct Answer: Use the lowest concentration that maintains pH control to avoid catalysis of degradation

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