Introduction: Applications of buffers MCQs With Answer is an essential resource for B.Pharm students preparing for exams and practicals. This concise guide explores buffer systems, pH control, Henderson-Hasselbalch calculations, buffer capacity, and real-world pharmaceutical applications such as formulation stability, parenterals, ophthalmic solutions, protein drug stabilization, and dissolution testing. Each question reinforces core concepts like buffer selection, ionic strength, common‑ion effects, sterilization impacts, and how pH influences drug ionization and solubility. Practicing these MCQs will strengthen problem-solving and decision-making skills required in formulation development and quality control. 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 act as an active drug substance
- To resist changes in pH when small amounts of acid or base are added
- To increase the viscosity of the formulation
- To serve as a preservative
Correct Answer: To resist changes in pH when small amounts of acid or base are added
Q2. Which two components make up a typical buffer system?
- A strong acid and a strong base
- An acid and its conjugate base or a base and its conjugate acid
- Two neutral salts
- A solvent and a surfactant
Correct Answer: An acid and its conjugate base or a base and its conjugate acid
Q3. The Henderson-Hasselbalch equation is primarily used to:
- Calculate osmolality
- Estimate the pH of a buffer from pKa and ratio of conjugate base to acid
- Determine drug partition coefficients
- Predict steric hindrance in molecules
Correct Answer: Estimate the pH of a buffer from pKa and ratio of conjugate base to acid
Q4. For effective buffering, the useful pH range of a buffer is approximately:
- pKa ± 3 units
- pKa ± 2 units
- pKa ± 1 unit
- pKa only
Correct Answer: pKa ± 1 unit
Q5. Buffer capacity is highest when:
- The concentration of acid is much greater than the base
- The concentration of base is much greater than the acid
- The concentrations of the weak acid and its conjugate base are equal
- The buffer is highly diluted
Correct Answer: The concentrations of the weak acid and its conjugate base are equal
Q6. How does dilution affect buffer capacity?
- Dilution increases buffer capacity
- Dilution has no effect on buffer capacity
- Dilution decreases buffer capacity
- Dilution converts buffer into a neutral solution
Correct Answer: Dilution decreases buffer capacity
Q7. Which buffer is most appropriate for maintaining physiological pH (~7.4) in many pharmaceutical formulations?
- Acetate buffer
- Phosphate buffer
- Citrate buffer
- Borate buffer
Correct Answer: Phosphate buffer
Q8. The common ion effect in buffers refers to:
- The generation of free radicals by buffers
- Precipitation of buffer salts
- Suppression of ionization of a weak acid or base by adding a common ion
- Increase in buffer viscosity
Correct Answer: Suppression of ionization of a weak acid or base by adding a common ion
Q9. Using Henderson-Hasselbalch, what is the pH when pKa = 4.76 and [A-]/[HA] = 1?
- 3.76
- 4.76
- 5.76
- 6.76
Correct Answer: 4.76
Q10. If acetic acid (pKa 4.76) buffer has [A-]/[HA] = 0.1, what is the approximate pH?
- 5.76
- 4.76
- 3.76
- 2.76
Correct Answer: 3.76
Q11. Which buffer is commonly used for solutions requiring pH around 4 to 6, such as some oral or topical products?
- Acetate buffer
- Phosphate buffer
- Borate buffer
- Ammonium buffer
Correct Answer: Acetate buffer
Q12. Which buffer component can chelate divalent metal ions and potentially affect formulation stability?
- Sodium chloride
- Citrate
- Sucrose
- Polysorbate
Correct Answer: Citrate
Q13. At the half-equivalence point during titration of a weak acid with strong base, the pH equals:
- Zero
- Half of the pKa
- The pKa of the acid
- The pKb of the conjugate base
Correct Answer: The pKa of the acid
Q14. Which buffer is preferred for many protein and vaccine formulations due to favorable stabilization properties around neutral pH?
- Glycine buffer at pH 2
- Histidine buffer near pH 6–7
- Acetate buffer at pH 4
- Bicarbonate buffer at pH 10
Correct Answer: Histidine buffer near pH 6–7
Q15. Which buffer system is volatile and therefore often used when downstream evaporation or mass spectrometry compatibility is required?
- Phosphate buffer
- Ammonium acetate buffer
- Borate buffer
- Citrate buffer
Correct Answer: Ammonium acetate buffer
Q16. Why must buffer ionic strength be considered in formulation development?
- Ionic strength only affects color
- Ionic strength influences drug solubility, protein stability, and electrostatic interactions
- Ionic strength eliminates preservatives
- Ionic strength is irrelevant for parenterals
Correct Answer: Ionic strength influences drug solubility, protein stability, and electrostatic interactions
Q17. Which buffer has pKa near 4.76 and is commonly used in acidic formulations?
- Phosphate
- Acetate
- Borate
- Tris
Correct Answer: Acetate
Q18. Which buffer system is likely to absorb CO2 from air and change pH on standing or autoclaving?
- Phosphate buffer
- Bicarbonate-carbonic acid buffer
- Acetate buffer
- Borate buffer
Correct Answer: Bicarbonate-carbonic acid buffer
Q19. Buffer selection for ophthalmic solutions must consider:
- Only cost of buffer
- pH compatibility with tear pH, isotonicity, irritation potential, and stability
- Buffer color and odor only
- Only antimicrobial activity
Correct Answer: pH compatibility with tear pH, isotonicity, irritation potential, and stability
Q20. Which buffer is most suitable for buffering near pH 9 in certain topical or chemical processes?
- Borate buffer
- Acetate buffer
- Citrate buffer
- Phosphate buffer
Correct Answer: Borate buffer
Q21. A primary pharmaceutical reason to use a buffer in an IV formulation is to:
- Enhance color
- Maintain pH to minimize pain and tissue irritation and to ensure drug stability
- Promote crystallization
- Reduce sterility requirements
Correct Answer: Maintain pH to minimize pain and tissue irritation and to ensure drug stability
Q22. Which statement about buffer pH and temperature is true?
- Buffer pH is completely independent of temperature
- Some buffers show pH changes with temperature due to temperature dependence of pKa
- All buffers become more basic as temperature increases
- Temperature only affects ionic strength, not pH
Correct Answer: Some buffers show pH changes with temperature due to temperature dependence of pKa
Q23. In choosing a buffer for a formulation that contains calcium, which buffer might cause precipitation issues?
- Phosphate buffer with calcium
- Acetate buffer with calcium
- Borate buffer with calcium
- Histidine buffer with calcium
Correct Answer: Phosphate buffer with calcium
Q24. How does pH influence drug ionization and thus solubility?
- pH does not affect ionization
- Ionization depends on pH relative to pKa and alters solubility and permeability
- All drugs are equally soluble at any pH
- Only temperature affects ionization
Correct Answer: Ionization depends on pH relative to pKa and alters solubility and permeability
Q25. Which buffer is commonly avoided in mass spectrometry due to non-volatility?
- Ammonium formate
- Ammonium acetate
- Phosphate buffer
- Volatile organic acid buffers
Correct Answer: Phosphate buffer
Q26. The buffer capacity quantitatively reflects:
- The concentration of buffer required for a drug
- The resistance of pH to change upon addition of acid or base
- The color stability of the formulation
- The number of ions present
Correct Answer: The resistance of pH to change upon addition of acid or base
Q27. Which buffer is widely used in dissolution testing and HPLC mobile phases when a non-volatile buffer is acceptable?
- Phosphate buffer
- Ammonium hydroxide buffer
- Formic acid buffer
- Ammonium acetate buffer
Correct Answer: Phosphate buffer
Q28. During formulation development, why is buffer concentration kept as low as feasible while maintaining capacity?
- To save costs only
- To reduce ionic strength, minimize incompatibilities, and limit toxicity while ensuring sufficient buffering
- Because higher concentration reduces pH control
- To increase microbial growth
Correct Answer: To reduce ionic strength, minimize incompatibilities, and limit toxicity while ensuring sufficient buffering
Q29. Which buffer component is likely to be problematic in sterile parenteral products due to toxicity at higher concentrations?
- Phosphate at moderate concentrations
- Borate at high concentrations
- Sodium chloride
- Water
Correct Answer: Borate at high concentrations
Q30. What effect does adding a large amount of strong acid to a buffer have compared with adding it to pure water?
- The pH change is greater in buffer than in pure water
- The pH change is smaller in buffer than in pure water
- The pH change is identical in both
- The buffer will precipitate
Correct Answer: The pH change is smaller in buffer than in pure water
Q31. Which buffer is commonly used for nucleic acid and electrophoresis applications and has pKa around 8.1?
- Tris buffer
- Acetate buffer
- Phosphate buffer
- Borate buffer
Correct Answer: Tris buffer
Q32. How does ionic strength influence apparent pKa values in buffer solutions?
- Ionic strength has no effect on pKa
- Ionic strength can shift apparent pKa by altering activity coefficients
- Ionic strength always increases pKa
- Ionic strength neutralizes acids
Correct Answer: Ionic strength can shift apparent pKa by altering activity coefficients
Q33. Which buffer is often used for formulations requiring acidic pH around 3?
- Citrate buffer
- Phosphate buffer
- Tris buffer
- Borate buffer
Correct Answer: Citrate buffer
Q34. A formulation requires pH 7.2 and you choose phosphate buffer (pKa2 ≈ 7.2). If the molar ratio [HPO4^2-]/[H2PO4^-] = 1, what is the expected pH?
- 6.2
- 7.2
- 8.2
- 9.2
Correct Answer: 7.2
Q35. Which buffer property is most critical when designing an ophthalmic product to avoid irritation?
- Buffer color
- Buffer pH and isotonicity close to tear fluid
- Buffer cost
- Buffer odor
Correct Answer: Buffer pH and isotonicity close to tear fluid
Q36. For precise pH adjustment of a buffer during preparation, the recommended practical approach is to:
- Mix equimolar amounts of acid and base always
- Add strong acid or base to the weak acid or base solution and measure pH until desired value is reached
- Heat the solution to change pH
- Add salts arbitrarily without measuring pH
Correct Answer: Add strong acid or base to the weak acid or base solution and measure pH until desired value is reached
Q37. Which phenomenon explains why a buffer near its pKa resists pH changes most effectively?
- Maximum salt solubility
- Equal concentrations of acid and base provide maximal neutralization capacity for added acids or bases
- Temperature effects
- Surface tension changes
Correct Answer: Equal concentrations of acid and base provide maximal neutralization capacity for added acids or bases
Q38. Which buffer is commonly used in topical pharmaceutical formulations like mouthwashes due to mild alkalinity and safety?
- Sodium bicarbonate buffer
- Hydrochloric acid buffer
- Strong base buffer
- Phosphoric acid buffer
Correct Answer: Sodium bicarbonate buffer
Q39. In analytical assays, why might phosphate buffers interfere with certain enzyme reactions?
- Phosphate always enhances all enzymes
- Phosphate can bind to enzyme active sites or alter metal cofactor availability and inhibit activity
- Phosphate changes color of reagents only
- Phosphate sterilizes the solution
Correct Answer: Phosphate can bind to enzyme active sites or alter metal cofactor availability and inhibit activity
Q40. The term ‘buffer range’ refers to:
- The range of temperatures a buffer can withstand
- The pH interval over which the buffer effectively resists pH change, approximately pKa ±1
- The concentration range of the buffer components
- The shelf life of the buffer
Correct Answer: The pH interval over which the buffer effectively resists pH change, approximately pKa ±1
Q41. Which buffer choice is most appropriate to stabilize a formulation at pH 5?
- Borate buffer
- Citrate or acetate buffer
- Tris buffer
- Ammonium buffer at pH 9
Correct Answer: Citrate or acetate buffer
Q42. What is the likely effect on drug stability if the formulation pH drifts away from the optimum pH during storage?
- No effect on drug stability
- Potential increase in degradation such as hydrolysis or oxidation depending on pH sensitivity
- Only color changes will occur
- Drug will become more potent
Correct Answer: Potential increase in degradation such as hydrolysis or oxidation depending on pH sensitivity
Q43. Which buffer system would be least suitable for a formulation that must be sterile and filtered through a 0.22 μm membrane requiring low particulate and metal contaminants?
- Buffered with volatile ammonium salts
- Buffered with sterile pharmaceutical-grade salts like phosphate made from high-purity reagents
- Buffered with impure crude salts containing insoluble particulates
- Buffered with ultrapure reagents and filtered
Correct Answer: Buffered with impure crude salts containing insoluble particulates
Q44. Which buffer is commonly used in vaccine formulations to provide stability and low toxicity?
- Histidine buffer
- Strong mineral acid buffer
- High concentration phosphate at extreme pH
- Undiluted organic solvent
Correct Answer: Histidine buffer
Q45. The term ‘buffer capacity’ can be qualitatively increased by:
- Decreasing the total buffer concentration
- Increasing the total buffer concentration while maintaining desired pH
- Evaporating solvent
- Adding organic dyes
Correct Answer: Increasing the total buffer concentration while maintaining desired pH
Q46. Which of the following is true regarding buffer selection for HPLC methods coupled to mass spectrometry?
- Use non-volatile buffers like phosphate for best MS sensitivity
- Prefer volatile buffers like ammonium acetate or formate to avoid ion source contamination
- Buffer choice has no effect on MS performance
- Any surfactant-based buffer is ideal
Correct Answer: Prefer volatile buffers like ammonium acetate or formate to avoid ion source contamination
Q47. During autoclaving, which buffer type is most likely to undergo pH change due to loss or gain of CO2?
- Bicarbonate buffer
- Phosphate buffer
- Acetate buffer
- Borate buffer
Correct Answer: Bicarbonate buffer
Q48. How does buffer pH affect preservative efficacy in multi-dose pharmaceutical products?
- Preservative efficacy is pH-independent
- Preservatives often have optimal activity at specific pH ranges, so buffer pH can increase or decrease antimicrobial effectiveness
- Buffers destroy all preservatives
- Buffers convert preservatives into active drugs
Correct Answer: Preservatives often have optimal activity at specific pH ranges, so buffer pH can increase or decrease antimicrobial effectiveness
Q49. In controlled release systems where pH triggers drug release, buffers are used to:
- Only color the dosage form
- Create a microenvironmental pH that triggers polymer swelling or erosion and controls release
- Increase tablet hardness only
- Reduce the need for excipients
Correct Answer: Create a microenvironmental pH that triggers polymer swelling or erosion and controls release
Q50. Which buffer would be a logical first choice for an oral rinse designed to neutralize acids in the mouth and be safe for mucosal tissues?
- Concentrated hydrochloric acid solution
- Sodium bicarbonate buffer
- Strong alkaline buffer at pH 12
- High concentration phosphate buffer at pH 2
Correct Answer: Sodium bicarbonate buffer

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