Buffers in pharmaceutical systems MCQs With Answer offers B.Pharm students a focused, Student-friendly post to buffer solutions, pH control, buffering agents, and buffer capacity as applied to pharmaceutical formulations. This concise guide covers buffer preparation, Henderson-Hasselbalch calculations, influence of ionic strength and temperature, and practical uses in parenteral, ophthalmic, and topical products. Ideal for exam prep, the content emphasizes real-world examples, buffer selection criteria, and stability considerations in drug development. Improve your problem-solving with targeted objective questions that reinforce theory and calculations. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is the primary function of a buffer in pharmaceutical formulations?
- To increase solubility of an active ingredient
- To maintain a stable pH when small amounts of acid or base are added
- To act as a preservative against microbial growth
- To enhance drug absorption through membranes
Correct Answer: To maintain a stable pH when small amounts of acid or base are added
Q2. Which equation relates pH, pKa, and the ratio of conjugate base to acid in a buffer?
- Van’t Hoff equation
- Henderson-Hasselbalch equation
- Arrhenius equation
- Gibbs free energy equation
Correct Answer: Henderson-Hasselbalch equation
Q3. For a buffer containing acetic acid (pKa 4.76), at pH 4.76 the ratio of acetate to acetic acid is:
- 10:1
- 1:10
- 1:1
- 100:1
Correct Answer: 1:1
Q4. Buffer capacity is highest when:
- pH is far from the pKa of the buffering system
- the concentration of buffer components is very low
- the pH equals the pKa and buffer concentration is high
- temperature is elevated significantly
Correct Answer: the pH equals the pKa and buffer concentration is high
Q5. Which of the following is a Good’s buffer commonly used in biochemical and pharmaceutical research?
- Sodium chloride
- HEPES
- Hydrochloric acid
- Sucrose
Correct Answer: HEPES
Q6. The Henderson-Hasselbalch equation for a weak acid HA is pH = pKa + log([A-]/[HA]). If pKa = 7.2 and pH = 6.2, what is [A-]/[HA]?
- 10
- 0.1
- 1
- 100
Correct Answer: 0.1
Q7. Which buffer system is most relevant for maintaining physiological pH in plasma?
- Acetate buffer
- Phosphate buffer
- Bicarbonate-carbonic acid buffer
- Citrate buffer
Correct Answer: Bicarbonate-carbonic acid buffer
Q8. The common-ion effect in buffers refers to:
- An ion shared between buffer components decreasing ionization of a weak acid or base
- A buffer’s incompatibility with salts
- Heat generated when buffers are mixed
- Formation of precipitates in buffer solutions
Correct Answer: An ion shared between buffer components decreasing ionization of a weak acid or base
Q9. Which parameter directly affects the activity coefficients and therefore the effective pH of a buffer?
- Ionic strength
- Molecular weight of solute
- Viscosity
- Color of solution
Correct Answer: Ionic strength
Q10. When preparing a buffer for an ophthalmic solution, the most critical consideration is:
- Optimal buffer pH matches tear pH to ensure comfort and minimize irritation
- Buffer must be extremely concentrated to prevent any pH change
- Using only strong acids as buffers
- Ensuring the buffer is colored for patient acceptance
Correct Answer: Optimal buffer pH matches tear pH to ensure comfort and minimize irritation
Q11. Which buffer would you choose for a formulation requiring pH ~ 7.4 and minimal interference with biochemical assays?
- Acetate buffer
- Citrate buffer
- Phosphate buffer
- Formic acid buffer
Correct Answer: Phosphate buffer
Q12. Buffer capacity (β) is defined as:
- Change in pH per added mole of acid
- Amount of strong acid or base needed to change the pH by one unit per liter
- Concentration of buffer components only
- The pKa value of the buffer
Correct Answer: Amount of strong acid or base needed to change the pH by one unit per liter
Q13. A buffer will resist pH changes best when the ratio [A-]/[HA] is between:
- 0.01 and 0.1
- 0.5 and 2
- 10 and 100
- 100 and 1000
Correct Answer: 0.5 and 2
Q14. Which of the following effects is commonly observed when buffers are diluted significantly?
- Buffer pH always shifts toward neutrality
- Buffer capacity decreases
- Buffer pKa increases dramatically
- Ionic strength becomes infinite
Correct Answer: Buffer capacity decreases
Q15. The Henderson-Hasselbalch equation assumes which of the following approximations?
- Activity coefficients equal one (activities ≈ concentrations)
- Temperature changes are large
- Strong acids only
- No conjugate base present
Correct Answer: Activity coefficients equal one (activities ≈ concentrations)
Q16. Which buffer pair is typically used for acidic drugs requiring storage around pH 4?
- Phosphate buffer (pKa ~7.2)
- Acetate buffer (pKa ~4.76)
- Bicarbonate buffer (pKa ~6.1)
- HEPES buffer (pKa ~7.5)
Correct Answer: Acetate buffer (pKa ~4.76)
Q17. In parenteral formulations, buffer selection must also consider which key factor?
- Potential toxicity or metabolic load of buffer components
- Buffer color
- Buffer smell
- Ease of autoclaving only
Correct Answer: Potential toxicity or metabolic load of buffer components
Q18. Which statement about phosphate buffers is true?
- They cannot be used above pH 5
- They have multiple pKa values and are useful over a wide pH range
- They always precipitate in the presence of calcium
- They are strong acids and not suitable as buffers
Correct Answer: They have multiple pKa values and are useful over a wide pH range
Q19. Temperature changes affect buffers mainly by:
- Altering the pKa of the buffering components
- Changing the molecular weight of the buffer
- Causing buffers to become colored
- Converting buffers into salts permanently
Correct Answer: Altering the pKa of the buffering components
Q20. Which buffer system is commonly used in injectable formulations but must be compatible with CO2 equilibration?
- Acetate buffer
- Bicarbonate buffer
- Tris buffer
- Citrate buffer
Correct Answer: Bicarbonate buffer
Q21. When designing a buffer for a drug that degrades at high pH, you should:
- Choose a buffer with pKa well above drug’s instability pH
- Match buffer pH close to the drug’s stability optimum and avoid buffer catalysts
- Use the strongest possible base to ensure maximal stability
- Ignore ionic strength considerations
Correct Answer: Match buffer pH close to the drug’s stability optimum and avoid buffer catalysts
Q22. The buffer index is another term used to describe:
- Buffer pH
- Buffer capacity
- Buffer concentration only
- Buffer temperature sensitivity
Correct Answer: Buffer capacity
Q23. If you need a buffer at pH 3.8, which buffer system is most suitable?
- Acetate buffer (pKa 4.76)
- Citrate buffer (pKa ~3.1, 4.76, 5.4 multiple pKas)
- Phosphate buffer (pKa 7.2)
- HEPES buffer (pKa 7.5)
Correct Answer: Citrate buffer (pKa ~3.1, 4.76, 5.4 multiple pKas)
Q24. Which method is best to adjust pH precisely when preparing buffers in the lab?
- Estimating volumes by eye
- Using pH meter and incremental additions of acid or base
- Heating solution to boil
- Adding powdered buffer salts without measurement
Correct Answer: Using pH meter and incremental additions of acid or base
Q25. In buffer preparation, why might one add inert salts like NaCl?
- To change color of solution
- To adjust ionic strength and simulate physiological conditions
- To increase buffer pKa
- To eliminate the need for pH adjustment
Correct Answer: To adjust ionic strength and simulate physiological conditions
Q26. For Henderson-Hasselbalch use, which concentrations should ideally be used?
- Total mass of solute only
- Activities of acid and base species or concentrations when activities ≈ concentrations
- Molar mass of solvent
- Volume of container only
Correct Answer: Activities of acid and base species or concentrations when activities ≈ concentrations
Q27. Which buffer is unsuitable for use at very low ionic strength biological assays due to its zwitterionic nature?
- HEPES
- Sodium acetate
- Sodium phosphate
- Hydrochloric acid
Correct Answer: HEPES
Q28. The term “isoionic point” in buffer chemistry refers to:
- pH where net electrical charge of a buffer molecule is zero
- Temperature at which buffer evaporates
- pH where buffer capacity is zero
- Concentration where buffer precipitates
Correct Answer: pH where net electrical charge of a buffer molecule is zero
Q29. A buffer’s resistance to pH change upon addition of acid is proportional to:
- The concentration of the conjugate base
- The molecular weight of the acid
- The color of the solution
- The ambient light intensity
Correct Answer: The concentration of the conjugate base
Q30. Which buffer component may chelate metal ions and affect drug stability?
- Sodium chloride
- Citrate
- Glucose
- Glycerol
Correct Answer: Citrate
Q31. In preparing a buffer, what does pKa represent?
- The pH at which half of the acid is dissociated
- The total concentration of buffer components
- The boiling point of the buffer solution
- The ionic strength of the solution
Correct Answer: The pH at which half of the acid is dissociated
Q32. Which buffer is often avoided in formulations requiring metal ions due to precipitation issues?
- Phosphate buffer
- Acetate buffer
- Tris buffer
- Buffer-free water
Correct Answer: Phosphate buffer
Q33. For a buffer system of HA/A-, what happens when a strong acid is added?
- HA is consumed and A- concentration decreases
- A- converts to HA increasing HA concentration and resisting pH change
- Buffer instantly becomes neutral
- Temperature drastically decreases
Correct Answer: A- converts to HA increasing HA concentration and resisting pH change
Q34. Which analytical instrument is essential for accurate buffer pH measurement?
- Spectrophotometer
- pH meter with calibrated electrode
- Centrifuge
- Mass spectrometer
Correct Answer: pH meter with calibrated electrode
Q35. If you need to increase the buffer pH slightly, which practical step would you use?
- Add a small amount of strong acid
- Add a small amount of the conjugate base
- Boil the solution vigorously
- Store the buffer in sunlight
Correct Answer: Add a small amount of the conjugate base
Q36. Which buffer is most suitable for formulations intended for nasal delivery requiring pH around 6.0?
- Acetate buffer
- Hydrochloric acid solution
- Strong alkali solution
- Metallic buffer
Correct Answer: Acetate buffer
Q37. The presence of organic solvents in a buffer can affect:
- Only the buffer color
- pKa values and buffer capacity
- The pH meter calibration never
- Buffer’s electrical conductivity only
Correct Answer: pKa values and buffer capacity
Q38. A buffer’s effective pH range is typically within:
- ±0.5 pH units of its pKa
- ±5.0 pH units of its pKa
- Only at pH equal to 7
- Anywhere regardless of pKa
Correct Answer: ±0.5 pH units of its pKa
Q39. Which buffer system is commonly employed in oral liquid pharmaceuticals to mask taste and maintain stability at acidic pH?
- Phosphate buffer at pH 8
- Citrate or acetate buffers at acidic pH
- Bicarbonate buffer at pH 10
- Unbuffered water
Correct Answer: Citrate or acetate buffers at acidic pH
Q40. When designing a buffer for protein formulations, what is a major consideration?
- Protein solubility and stability in the chosen buffer at the working pH
- Using the highest possible ionic strength regardless of protein behavior
- Always using phosphate buffer only
- Ensuring buffer contains strong oxidizers
Correct Answer: Protein solubility and stability in the chosen buffer at the working pH
Q41. The buffer capacity formula β = 2.303 × C × (Ka × [H+])/(Ka + [H+])^2 is used to:
- Calculate ionic strength
- Estimate buffer capacity as a function of pH and total concentration
- Measure the boiling point elevation
- Compute molar mass of buffer components
Correct Answer: Estimate buffer capacity as a function of pH and total concentration
Q42. Which buffer is often avoided in cell culture due to CO2 dependence and variable pH under atmospheric CO2?
- HEPES
- Bicarbonate buffer
- Acetate buffer
- Tris buffer
Correct Answer: Bicarbonate buffer
Q43. Which is a potential drawback of using strong buffer concentrations in formulations?
- Enhanced microbial stability always
- Potential for increased ionic strength leading to protein aggregation or precipitation
- Guaranteed improved drug solubility
- Reduction of all excipient interactions
Correct Answer: Potential for increased ionic strength leading to protein aggregation or precipitation
Q44. A buffer composed of NH4+/NH3 (pKa ~9.25) will be most effective at:
- pH ~1
- pH ~9.25
- pH ~4
- pH ~12
Correct Answer: pH ~9.25
Q45. How does dilution affect the Henderson-Hasselbalch relationship when activity coefficients change significantly?
- Dilution has no effect ever
- Apparent pH may shift because activities deviate from concentrations
- pKa becomes zero
- All buffers become stronger
Correct Answer: Apparent pH may shift because activities deviate from concentrations
Q46. In titration of a weak acid with a strong base, the point at which pH = pKa corresponds to:
- The equivalence point
- Half-neutralization point
- Initial pH only
- Complete precipitation
Correct Answer: Half-neutralization point
Q47. Which buffer is commonly used in topical formulations where metal ion chelation must be avoided?
- Citrate-based buffer
- Phosphate buffer without chelators
- Buffers containing EDTA
- Highly concentrated bicarbonate
Correct Answer: Phosphate buffer without chelators
Q48. When monitoring buffer stability over time, which parameter is most important to track?
- pH drift and any precipitate formation
- Buffer bottle color only
- Date on the cap
- Temperature in winter only
Correct Answer: pH drift and any precipitate formation
Q49. Which is a reason to choose acetate buffer over phosphate buffer in certain formulations?
- Acetate has pKa closer to acidic drug pH requirements and less propensity to precipitate with calcium
- Acetate always increases viscosity
- Phosphate never affects protein stability
- Acetate is a strong oxidizing agent
Correct Answer: Acetate has pKa closer to acidic drug pH requirements and less propensity to precipitate with calcium
Q50. For an MCQ testing Henderson-Hasselbalch calculation, what supporting data should be provided to ensure a solvable question?
- Only the buffer name without pKa or concentrations
- pKa value, total or component concentrations, and target pH or ratio
- The brand name of buffer solution
- Ambient humidity only
Correct Answer: pKa value, total or component concentrations, and target pH or ratio

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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