Adjustment of isotonicity MCQs With Answer

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Adjustment of isotonicity MCQs With Answer helps B. Pharm students master how to make ophthalmic, parenteral, and nasal formulations physiologically compatible. Understanding tonicity vs osmolarity, freezing point depression (cryoscopic method), sodium chloride equivalent (E-value), and White–Vincent/Sprowls methods is essential in pharmaceutics. Topics include 0.9% NaCl standards, -0.52°C isotonic freezing point, colligative properties, effects of hypertonic/hypotonic solutions (crenation, hemolysis), and choosing adjusters like NaCl, dextrose, mannitol, or boric acid (ophthalmics). You’ll also learn calculation shortcuts (0.009 × V − ΣwE), clinical tolerances (ophthalmic 0.6–2% NaCl equivalent), and pitfalls with penetrating solutes (urea, glycerol). Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the best definition of isotonicity in pharmaceutical solutions?

  • A solution having the same osmolarity as any reference solution
  • A solution that does not cause net water movement across a biological membrane
  • A solution with the same freezing point as pure water
  • A solution that has equal pH to body fluids

Correct Answer: A solution that does not cause net water movement across a biological membrane

Q2. Which dosage forms most critically require isotonicity adjustment?

  • Ophthalmic preparations
  • Parenteral injections
  • Nasal solutions
  • All of the above

Correct Answer: All of the above

Q3. The freezing point depression of an isotonic solution with blood plasma is approximately:

  • -0.20°C
  • -0.52°C
  • -1.86°C
  • -0.90°C

Correct Answer: -0.52°C

Q4. The approximate osmolarity of 0.9% w/v sodium chloride solution is:

  • ≈154 mOsm/L
  • ≈278 mOsm/L
  • ≈308 mOsm/L
  • ≈600 mOsm/L

Correct Answer: ≈308 mOsm/L

Q5. What cellular effect does a hypotonic solution have on red blood cells (RBCs)?

  • Crenation
  • No change
  • Hemolysis
  • Precipitation of hemoglobin

Correct Answer: Hemolysis

Q6. How does tonicity differ from osmolarity?

  • Tonicity and osmolarity are identical terms
  • Tonicity considers only electrolytes; osmolarity considers all solutes
  • Tonicity accounts for membrane permeability (effective osmolality); osmolarity does not
  • Osmolarity accounts for permeability; tonicity does not

Correct Answer: Tonicity accounts for membrane permeability (effective osmolality); osmolarity does not

Q7. Which method uses sodium chloride equivalent (E-value) to adjust isotonicity?

  • White–Vincent method
  • Sprowls method
  • E-value method
  • Cryoscopic method

Correct Answer: E-value method

Q8. The White–Vincent method primarily calculates:

  • The mass of NaCl to add directly to the formulation
  • The volume of water needed to prepare an isotonic solution of the drug
  • The pH range for isotonicity
  • The buffer capacity required for isotonicity

Correct Answer: The volume of water needed to prepare an isotonic solution of the drug

Q9. The Sprowls method is best described as:

  • A cryoscopic technique using direct freezing point measurement
  • A table-based extension of White–Vincent to reduce calculations
  • A buffer-based approach to isotonicity
  • An equation to convert osmolality to osmolarity

Correct Answer: A table-based extension of White–Vincent to reduce calculations

Q10. The cryoscopic method of isotonic adjustment relies on which colligative property?

  • Boiling point elevation
  • Vapor pressure lowering
  • Freezing point depression
  • Surface tension reduction

Correct Answer: Freezing point depression

Q11. In the White–Vincent method, the constant 111.1 represents:

  • The osmolarity (mOsm/L) of isotonic saline
  • The mL of isotonic solution containing 1 g of NaCl
  • The Liso constant for NaCl
  • The degree of dissociation for NaCl

Correct Answer: The mL of isotonic solution containing 1 g of NaCl

Q12. Which agent is commonly used to adjust isotonicity of ophthalmic solutions but is not suitable for IV use?

  • Boric acid
  • Mannitol
  • Sodium chloride
  • Dextrose

Correct Answer: Boric acid

Q13. Which statement about 1.9% boric acid solution is correct?

  • It is isotonic with tears but not isotonic with blood
  • It is isotonic with blood but not with tears
  • It is hypertonic to both tears and blood
  • It is hypotonic to both tears and blood

Correct Answer: It is isotonic with tears but not isotonic with blood

Q14. 5% dextrose solution (D5W) is best described as:

  • Isotonic and remains isotonic in vivo
  • Hypertonic and remains hypertonic in vivo
  • Iso-osmotic but becomes hypotonic in vivo as glucose is metabolized
  • Hypotonic and becomes hypertonic in vivo

Correct Answer: Iso-osmotic but becomes hypotonic in vivo as glucose is metabolized

Q15. Which solute is penetrating and can cause hemolysis even if the solution is iso-osmotic?

  • Sodium chloride
  • Mannitol
  • Urea
  • Boric acid (ophthalmic)

Correct Answer: Urea

Q16. Acceptable NaCl equivalent range for ophthalmic solutions (patient comfort) is approximately:

  • 0.2–0.4% NaCl
  • 0.6–2.0% NaCl
  • 2–4% NaCl
  • 4–6% NaCl

Correct Answer: 0.6–2.0% NaCl

Q17. For IV infusions, the desirable osmolarity range is closest to:

  • 100–150 mOsm/L
  • 200–240 mOsm/L
  • 275–310 mOsm/L
  • 450–600 mOsm/L

Correct Answer: 275–310 mOsm/L

Q18. How much NaCl must be added to 30 mL of a 1% w/v drug solution (drug E = 0.18) to make it isotonic? (0.9% basis)

  • 0.162 g
  • 0.216 g
  • 0.270 g
  • 0.324 g

Correct Answer: 0.216 g

Q19. How much NaCl must be added to 100 mL of a 2% w/v drug solution (drug E = 0.18)?

  • 0.18 g
  • 0.36 g
  • 0.54 g
  • 0.90 g

Correct Answer: 0.54 g

Q20. For 50 mL containing Drug A 1% (E=0.12) and Drug B 2% (E=0.08), NaCl to add is:

  • 0.17 g
  • 0.22 g
  • 0.31 g
  • 0.45 g

Correct Answer: 0.31 g

Q21. If the calculated NaCl to add is negative, it indicates:

  • The solution is hypotonic and needs more NaCl
  • The solution is hypertonic and should be diluted or adjusted with water/isotonic vehicle
  • Calculation error; repeat steps
  • Tonicity is unaffected by excipients

Correct Answer: The solution is hypertonic and should be diluted or adjusted with water/isotonic vehicle

Q22. Which relationship is correct for freezing point depression (ΔTf)?

  • ΔTf ∝ total molality × van’t Hoff factor
  • ΔTf ∝ temperature
  • ΔTf ∝ pressure
  • ΔTf ∝ molecular weight squared

Correct Answer: ΔTf ∝ total molality × van’t Hoff factor

Q23. The cryoscopic constant (Kf) for water is approximately:

  • 0.52°C·kg/mol
  • 1.86°C·kg/mol
  • 2.43°C·kg/mol
  • 0.93°C·kg/mol

Correct Answer: 1.86°C·kg/mol

Q24. If a formulation accounts for ΔTf = 0.28°C, the additional NaCl equivalent ΔTf needed to reach isotonicity (0.52°C) is closest to which % NaCl?

  • 0.24% NaCl
  • 0.41% NaCl
  • 0.52% NaCl
  • 0.76% NaCl

Correct Answer: 0.41% NaCl

Q25. Buffers in a formulation:

  • Do not influence tonicity
  • May contribute to tonicity and must be included in calculations
  • Always reduce tonicity
  • Always increase osmolarity beyond isotonic

Correct Answer: May contribute to tonicity and must be included in calculations

Q26. Which preparation is intentionally hypertonic to draw fluid from the cornea in edema?

  • 0.9% NaCl eye drops
  • 5% NaCl eye drops
  • 0.6% NaCl eye drops
  • 5% dextrose eye drops

Correct Answer: 5% NaCl eye drops

Q27. Which is a non-electrolyte commonly used to adjust isotonicity?

  • Calcium chloride
  • Dextrose
  • Sodium bicarbonate
  • Potassium chloride

Correct Answer: Dextrose

Q28. The equation relating osmotic pressure to concentration is:

  • Henderson–Hasselbalch equation
  • van’t Hoff’s equation (π = iMRT)
  • Arrhenius equation
  • Michaelis–Menten equation

Correct Answer: van’t Hoff’s equation (π = iMRT)

Q29. In the White–Vincent method, after calculating V (mL) for isotonicity with water, the next step is to:

  • Add solid NaCl up to the final volume
  • Make up to the final volume with isotonic vehicle (e.g., 0.9% NaCl)
  • Adjust pH to 7.4
  • Boil and cool to room temperature

Correct Answer: Make up to the final volume with isotonic vehicle (e.g., 0.9% NaCl)

Q30. Osmolality differs from osmolarity in that it is expressed as:

  • Osmoles per liter of solution
  • Osmoles per kilogram of solvent
  • Grams per liter of solute
  • Moles per liter of solvent

Correct Answer: Osmoles per kilogram of solvent

Q31. The approximate osmolarity of 0.45% (half-normal) saline is:

  • ≈154 mOsm/L
  • ≈308 mOsm/L
  • ≈450 mOsm/L
  • ≈90 mOsm/L

Correct Answer: ≈154 mOsm/L

Q32. Which tonicity deviation is most likely to cause pain, hemolysis, and thrombophlebitis on IV administration?

  • Slight hypertonicity
  • Marked hypotonicity
  • Isotonicity
  • Iso-osmotic with penetrating solutes

Correct Answer: Marked hypotonicity

Q33. The general E-value formula for NaCl to add is:

  • Amount NaCl (g) = 0.009 × V (mL) − Σ(wi × Ei)
  • Amount NaCl (g) = 0.9 × V (mL) − Σ(wi ÷ Ei)
  • Amount NaCl (g) = V ÷ (ΣEi)
  • Amount NaCl (g) = 0.0052 × V (mL) + Σ(wi × Ei)

Correct Answer: Amount NaCl (g) = 0.009 × V (mL) − Σ(wi × Ei)

Q34. A 1.9% w/v boric acid ophthalmic solution is:

  • Generally acceptable as isotonic with tears
  • Isotonic with blood plasma
  • Hypertonic to tears
  • Hypotonic to tears

Correct Answer: Generally acceptable as isotonic with tears

Q35. Choose the correct pair:

  • Tonicity — effective osmolality across a biological membrane
  • Tonicity — molality per kg solvent
  • Osmolality — affected by membrane permeability
  • Osmolarity — measured only by freezing point

Correct Answer: Tonicity — effective osmolality across a biological membrane

Q36. Which agent should not be used as an isotonicity adjuster in injectable formulations?

  • Sodium chloride
  • Mannitol
  • Dextrose
  • Boric acid

Correct Answer: Boric acid

Q37. For intrathecal injections, isotonicity requirements are best described as:

  • Loose; wide deviation tolerated
  • Moderate; slight deviation tolerated
  • Strict; solutions should be as close to CSF isotonicity as possible
  • Irrelevant; only sterility matters

Correct Answer: Strict; solutions should be as close to CSF isotonicity as possible

Q38. A key advantage of the Sprowls method is that it:

  • Eliminates the need for E-values entirely
  • Provides tabulated V values (mL per gram) to simplify volume calculations
  • Directly measures osmolarity without instruments
  • Uses buffer capacity to fix isotonicity

Correct Answer: Provides tabulated V values (mL per gram) to simplify volume calculations

Q39. The freezing point of normal tears is closest to:

  • -0.10°C
  • -0.52°C to -0.55°C
  • -1.86°C
  • 0°C

Correct Answer: -0.52°C to -0.55°C

Q40. Which statement about osmotically effective particles is correct?

  • Penetrating solutes exert sustained osmotic gradients
  • Non-penetrating solutes predominantly determine tonicity
  • All solutes have equal effect on tonicity
  • Only electrolytes affect tonicity

Correct Answer: Non-penetrating solutes predominantly determine tonicity

Q41. A 100 mL solution contains 2 g of a drug with E = 0.30. Its tonicity relative to plasma is:

  • Hypertonic
  • Hypotonic
  • Isotonic
  • Iso-osmotic but hypotonic

Correct Answer: Hypotonic

Q42. In White–Vincent, if V (required isotonic volume) is 35 mL and the target final volume is 50 mL, add how much 0.9% NaCl solution?

  • 15 mL
  • 35 mL
  • 50 mL
  • 0 mL

Correct Answer: 15 mL

Q43. In the E-value method, what is the E of NaCl?

  • 0.18
  • 0.90
  • 1.00
  • 3.40

Correct Answer: 1.00

Q44. Which provides more osmoles per gram in solution?

  • Dextrose
  • Sodium chloride
  • Urea
  • Boric acid

Correct Answer: Sodium chloride

Q45. Why must the hydration state (e.g., monohydrate) of salts be considered during isotonicity calculations?

  • It changes the degree of ionization
  • It affects molecular weight and thus E-value/osmolar contribution
  • It changes the freezing point of water
  • It is irrelevant for colligative properties

Correct Answer: It affects molecular weight and thus E-value/osmolar contribution

Q46. A practical step in the cryoscopic method is to:

  • Measure the solution’s freezing point and adjust to about -0.52°C
  • Assume ΔTf from label claims
  • Adjust pH to 7.4 before measuring ΔTf
  • Ignore excipients’ contribution to ΔTf

Correct Answer: Measure the solution’s freezing point and adjust to about -0.52°C

Q47. If a 100 mL formulation already provides 0.9 g NaCl equivalent from drug and excipients, how much NaCl should be added?

  • 0.90 g
  • 0.45 g
  • 0.00 g
  • 1.80 g

Correct Answer: 0.00 g

Q48. To avoid altering ionic strength while adjusting isotonicity, which is most suitable?

  • Sodium chloride
  • Potassium chloride
  • Mannitol
  • Sodium bicarbonate

Correct Answer: Mannitol

Q49. For neonatal ophthalmic formulations, isotonicity should be:

  • Less critical than in adults
  • Targeted close to isotonic to minimize irritation and risk
  • Replaced by hypertonic drops for stability
  • Ignored if sterile

Correct Answer: Targeted close to isotonic to minimize irritation and risk

Q50. How much NaCl is needed to isotonic-adjust 10 mL containing 0.5 g drug (E = 0.13)?

  • 0.025 g
  • 0.065 g
  • 0.090 g
  • 0.130 g

Correct Answer: 0.025 g

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