Buffered isotonic solutions MCQs With Answer

Buffered isotonic solutions MCQs With Answer: This focused introduction for B. Pharm students explains principles and applications of buffered isotonic solutions used in parenteral, ophthalmic, and pharmaceutical formulations. You will review buffer components, pH control, buffer capacity, isotonicity calculations, Henderson-Hasselbalch applications, NaCl equivalents, osmolarity vs tonicity, selection of phosphate or acetate buffers, and stability and compatibility considerations. Clear practical examples and calculation approaches help consolidate formulation skills and quality control knowledge. These MCQs are designed to deepen understanding beyond basic definitions and prepare you for exams and lab practice. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What defines a buffered isotonic solution in pharmaceutics?

• A solution that resists pH change and has the same osmotic pressure as plasma
• A solution that changes pH on dilution and is hyperosmotic to plasma
• A solution containing only electrolytes with no pH control
• A solution that is sterile but hypotonic to plasma

Correct Answer: A solution that resists pH change and has the same osmotic pressure as plasma

Q2. Which buffer system is most commonly used for intravenous parenteral solutions?

• Acetate buffer
• Phosphate buffer
• Carbonate buffer
• Tris buffer

Correct Answer: Phosphate buffer

Q3. The Henderson-Hasselbalch equation is primarily used to:

• Calculate isotonicity based on freezing point depression
• Determine pH from pKa and the ratio of conjugate base to acid
• Measure osmotic pressure directly
• Estimate buffer capacity without concentration data

Correct Answer: Determine pH from pKa and the ratio of conjugate base to acid

Q4. Buffer capacity is highest when:

• pH is far from pKa by more than 3 units
• Concentrations of acid and conjugate base are equal and pH ≈ pKa
• The buffer is extremely dilute
• Only the conjugate base is present

Correct Answer: Concentrations of acid and conjugate base are equal and pH ≈ pKa

Q5. The useful buffer range is generally described as:

• pKa ± 3 units
• pKa ± 2 units
• pKa ± 1 unit
• Any pH value regardless of pKa

Correct Answer: pKa ± 1 unit

Q6. Isotonicity refers to which of the following?

• Same pH as blood
• Same osmotic pressure as blood serum
• Same ionic composition as blood
• Same viscosity as blood

Correct Answer: Same osmotic pressure as blood serum

Q7. What is the approximate osmolarity of human plasma that isotonic solutions target?

• 150 mOsm/L
• 290–310 mOsm/L
• 500–600 mOsm/L
• 50–100 mOsm/L

Correct Answer: 290–310 mOsm/L

Q8. The NaCl equivalent (E-value) is used to:

• Calculate pH of buffered solutions
• Convert the tonicity contribution of a solute to equivalent NaCl percentage
• Determine buffer pKa
• Measure antimicrobial activity in solutions

Correct Answer: Convert the tonicity contribution of a solute to equivalent NaCl percentage

Q9. Which method estimates isotonicity by measuring freezing point depression?

• Osmometry / cryoscopy
• Titration
• pH meter analysis
• Conductivity testing

Correct Answer: Osmometry / cryoscopy

Q10. When adjusting tonicity for an ophthalmic solution, a common isotonic agent used is:

• 0.9% sodium chloride
• 5% ethanol
• 10% glycerin
• 2% benzyl alcohol

Correct Answer: 0.9% sodium chloride

Q11. Why are phosphate buffers widely used in parenteral formulations?

• They have no interaction with calcium or magnesium
• They have good buffering capacity near physiological pH and are biocompatible
• They are volatile and easily removed
• They are highly antimicrobial

Correct Answer: They have good buffering capacity near physiological pH and are biocompatible

Q12. Which statement about isotonic vs iso-osmotic is correct?

• Iso-osmotic always equals isotonic for biological systems
• Iso-osmotic means same osmotic concentration but not necessarily same biological effect (tonicity)
• Isotonic is only used for non-aqueous systems
• They are interchangeable terms in pharmaceutics

Correct Answer: Iso-osmotic means same osmotic concentration but not necessarily same biological effect (tonicity)

Q13. Which buffer would be inappropriate for a solution containing calcium ions due to precipitation risk?

• Sodium phosphate buffer
• Tris buffer
• Acetate buffer
• Histidine buffer

Correct Answer: Sodium phosphate buffer

Q14. The Henderson-Hasselbalch equation: pH = pKa + log([A–]/[HA]) assumes which of the following?

• Complete dissociation of strong acids
• Equilibrium between weak acid and conjugate base
• No ionic strength effects ever
• Temperature independence of pKa

Correct Answer: Equilibrium between weak acid and conjugate base

Q15. Which factor reduces buffer capacity?

• High total concentration of buffer components
• Large difference between pH and pKa
• Equal concentrations of acid and base
• Presence of a strong electrolyte that does not react

Correct Answer: Large difference between pH and pKa

Q16. For preparing a 0.9% NaCl isotonic solution, which ionic strength consideration is most important?

• Total molarity of non-ionic solutes
• Total osmotic contribution from all solutes including electrolytes
• pH only
• Colour of the solution

Correct Answer: Total osmotic contribution from all solutes including electrolytes

Q17. Which calculation method is commonly used to adjust isotonicity for small-volume parenterals?

• Henderson-Hasselbalch only
• Pereira’s freezing point method and NaCl equivalents
• Titration to neutral pH
• Thermal gravimetric analysis

Correct Answer: Pereira’s freezing point method and NaCl equivalents

Q18. The presence of CO2 in buffer systems primarily affects:

• Osmolarity only
• pH through formation of carbonic acid and bicarbonate equilibrium
• Sterility of the solution
• Color of the solution

Correct Answer: pH through formation of carbonic acid and bicarbonate equilibrium

Q19. Which buffer is preferred for ophthalmic solutions due to minimal irritation and physiological compatibility?

• Phosphate buffer
• Strong mineral acid buffer
• Sodium hydroxide-only buffer
• Formaldehyde buffer

Correct Answer: Phosphate buffer

Q20. Osmolarity differs from osmotic pressure in that osmolarity is:

• A measure of pressure exerted by particles across a membrane
• The concentration of osmotically active particles per liter of solution
• Always equal to tonicity in biological fluids
• Irrelevant for formulating parenteral solutions

Correct Answer: The concentration of osmotically active particles per liter of solution

Q21. A buffer with pKa 7.4 is most effective at which pH range?

• pH 4.4–5.4
• pH 6.4–8.4
• pH 8.4–10.4
• pH 1.4–3.4

Correct Answer: pH 6.4–8.4

Q22. Adding salt (NaCl) to a buffer solution primarily affects:

• Buffer pKa dramatically
• Ionic strength and osmolarity, which can influence activity coefficients
• Only the color
• Buffer concentration remains irrelevant

Correct Answer: Ionic strength and osmolarity, which can influence activity coefficients

Q23. Which statement about autoclaving buffered solutions is correct?

• Autoclaving never changes pH
• Autoclaving can change pH due to decomposition or CO2 loss/gain
• Autoclaving always increases buffer capacity
• Autoclaving is not used for parenteral solutions

Correct Answer: Autoclaving can change pH due to decomposition or CO2 loss/gain

Q24. In preparing a phosphate buffer, the conjugate pairs commonly used are:

• HCl and Cl–
• H2PO4– and HPO4^2–
• Acetic acid and sodium acetate only
• Ammonia and ammonium chloride

Correct Answer: H2PO4– and HPO4^2–

Q25. Which of the following is a correct reason to select acetate buffer over phosphate?

• Acetate buffer has better compatibility with calcium-containing solutions
• Acetate has buffering range close to pH 4–6 useful for certain drugs
• Acetate cannot be sterilized
• Acetate always increases viscosity

Correct Answer: Acetate has buffering range close to pH 4–6 useful for certain drugs

Q26. The E-value for a solute is used to calculate:

• The amount of solute equivalent to a given NaCl concentration for isotonicity
• The pKa of the solute
• The buffer capacity directly
• The solute’s antimicrobial potency

Correct Answer: The amount of solute equivalent to a given NaCl concentration for isotonicity

Q27. Which of the following agents is often used to render solutions hypotonic for specific clinical uses?

• Sucrose to increase tonicity
• Adding distilled water to lower osmolarity
• Adding extra NaCl to decrease osmolarity
• Adding glycerin to cause hypotonicity

Correct Answer: Adding distilled water to lower osmolarity

Q28. For parenteral buffers, the acceptable pH range is generally chosen based on:

• Formulator’s preference only
• Drug stability, tissue tolerance, and physiological pH
• Color stability exclusively
• Cost of buffer salts only

Correct Answer: Drug stability, tissue tolerance, and physiological pH

Q29. Which technique helps assess whether an ophthalmic preparation is isotonic?

• Visual inspection only
• Measuring freezing point depression or osmolarity
• Measuring color change on application
• Measuring pH only

Correct Answer: Measuring freezing point depression or osmolarity

Q30. A buffer’s pKa is temperature-dependent. Increasing temperature typically:

• Has no effect on pKa
• May change pKa and thus buffer pH at equilibrium
• Always increases pKa linearly
• Destroys buffer components instantly

Correct Answer: May change pKa and thus buffer pH at equilibrium

Q31. Which one is true about buffer dilution?

• Dilution has no effect on buffer capacity but changes pH
• Dilution reduces buffer capacity but pH remains similar if ratio unchanged
• Dilution increases ionic strength
• Dilution eliminates conjugate base

Correct Answer: Dilution reduces buffer capacity but pH remains similar if ratio unchanged

Q32. Why must the ionic strength of a buffer be considered in formulation?

• Ionic strength affects activity coefficients and the apparent pH and solubility of drugs
• Ionic strength only affects color
• Ionic strength prevents sterilization
• Ionic strength is irrelevant in parenteral formulations

Correct Answer: Ionic strength affects activity coefficients and the apparent pH and solubility of drugs

Q33. Which preservative’s activity can be strongly pH-dependent in buffered solutions?

• Benzalkonium chloride
• Sodium chloride
• Ultrapure water
• Glycerin

Correct Answer: Benzalkonium chloride

Q34. The cryoscopic constant (Kf) is used to:

• Calculate pH from pKa
• Relate freezing point depression to molal concentration for osmotic calculations
• Measure buffer capacity directly
• Determine microbial contamination

Correct Answer: Relate freezing point depression to molal concentration for osmotic calculations

Q35. A drug unstable at neutral pH might be best formulated in a buffer with pH:

• Close to the drug’s pKa where it is most stable
• Exactly pH 7.4 regardless of stability
• As acidic as possible without testing
• Only alkaline above pH 10

Correct Answer: Close to the drug’s pKa where it is most stable

Q36. Which statement is true about buffer selection for injectable formulations?

• Any buffer is acceptable if it gives the desired pH
• Buffer salts must be pharmacopeial grade and compatible with drug and excipients
• Buffers should be chosen for strong color properties
• Only organic buffers are allowed in injectables

Correct Answer: Buffer salts must be pharmacopeial grade and compatible with drug and excipients

Q37. What happens to the pH of an acetate buffer if excess strong acid is added?

• It becomes more alkaline
• It becomes more acidic but resists change relative to unbuffered solution
• It changes color instead of pH
• It precipitates immediately

Correct Answer: It becomes more acidic but resists change relative to unbuffered solution

Q38. The principal difference between osmolarity and tonicity is:

• Osmolarity considers all solute particles; tonicity considers only non-penetrating solutes that affect cell volume
• Tonicity is a laboratory-measured physical property while osmolarity is theoretical
• They are identical in all pharmaceutical contexts
• Osmolarity only applies to non-aqueous solutions

Correct Answer: Osmolarity considers all solute particles; tonicity considers only non-penetrating solutes that affect cell volume

Q39. Ringer’s lactate acts as an isotonic fluid partly because it contains:

• Only glucose
• Sodium, chloride, potassium, calcium and lactate which buffer blood pH
• High concentrations of albumin
• Strong acids only

Correct Answer: Sodium, chloride, potassium, calcium and lactate which buffer blood pH

Q40. Which approach helps maintain pH throughout shelf life of a buffered formulation?

• Using low concentration volatile buffers
• Selecting buffers resistant to CO2 absorption and degradation, and packaging to minimize gas exchange
• Leaving product open to air to equilibrate continuously
• Not using any buffer and relying on drug self-buffering

Correct Answer: Selecting buffers resistant to CO2 absorption and degradation, and packaging to minimize gas exchange

Q41. How is buffer capacity quantitatively related to concentration?

• Buffer capacity is inversely proportional to total buffer concentration
• Buffer capacity increases with increasing total concentration of acid and base
• Buffer capacity is independent of concentration
• Buffer capacity decreases with equal proportions of acid and base

Correct Answer: Buffer capacity increases with increasing total concentration of acid and base

Q42. An isotonic solution for intravenous use must avoid which of the following?

• pH within physiological range
• Large osmolality differences that cause hemolysis or fluid shifts
• Use of pharmacopoeial grade salts
• Proper sterility assurance

Correct Answer: Large osmolality differences that cause hemolysis or fluid shifts

Q43. Which buffer would be most suitable for maintaining pH around 5.0 in an oral liquid drug?

• Phosphate buffer with pKa 7.2
• Acetate buffer with pKa ≈ 4.76
• Tris buffer with pKa 8.1
• Carbonate buffer with pKa > 9

Correct Answer: Acetate buffer with pKa ≈ 4.76

Q44. The primary concern with using auxiliary buffering agents like citrate is:

• Their inability to dissolve
• Potential to chelate metal ions and affect drug stability
• They never affect tonicity
• They cannot be sterilized

Correct Answer: Potential to chelate metal ions and affect drug stability

Q45. Which statement about pH adjustment when preparing a buffer is correct?

• Always add strong acid to raise pH
• Adjust pH by adding small amounts of acid or base while monitoring with a calibrated pH meter
• Never measure pH; estimate from proportions only
• Only temperature adjustments can change pH

Correct Answer: Adjust pH by adding small amounts of acid or base while monitoring with a calibrated pH meter

Q46. When a drug is a weak base, how does pH influence its solubility and ionization in a buffer?

• Lower pH increases ionization and usually increases solubility
• Lower pH decreases ionization of a weak base
• pH has no effect on weak base ionization
• Higher pH always precipitates weak bases

Correct Answer: Lower pH increases ionization and usually increases solubility

Q47. Which test must be performed to confirm sterility and pH stability of a buffered parenteral?

• Only visual inspection
• Sterility testing and accelerated stability pH monitoring
• Only osmolarity check once
• Only NaCl titration

Correct Answer: Sterility testing and accelerated stability pH monitoring

Q48. The “isotonic adjustment factor” for a substance indicates:

• How much of the substance must be added to change color
• How to calculate the amount of substance required to make a solution isotonic compared to NaCl
• Its buffering capacity directly
• Its pKa value

Correct Answer: How to calculate the amount of substance required to make a solution isotonic compared to NaCl

Q49. Why is local tissue tolerance important when choosing buffer and pH for injectable formulations?

• Because buffer choice determines the colour only
• Because pH and buffer ions can cause pain, irritation, or tissue damage if outside tolerated ranges
• Because tissue tolerance is unrelated to pH
• Because it affects the formulation’s taste

Correct Answer: Because pH and buffer ions can cause pain, irritation, or tissue damage if outside tolerated ranges

Q50. A manufacturer wants to prepare a buffered isotonic infusion. Which integrated approach is best?

• Choose buffer with appropriate pKa and concentration, calculate tonicity using mOsm or NaCl equivalents, ensure compatibility and stability, and validate sterility
• Use only distilled water and no buffer
• Pick the cheapest salts without testing pH or tonicity
• Rely on visual clarity as the sole quality criterion

Correct Answer: Choose buffer with appropriate pKa and concentration, calculate tonicity using mOsm or NaCl equivalents, ensure compatibility and stability, and validate sterility

G S Sachin

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.

Mail- Sachin@pharmacyfreak.com