Isotonic solution calculations (freezing point method) MCQs With Answer

Introduction: Isotonic solution calculations (freezing point method) are essential in pharmaceutics for preparing safe ophthalmic and parenteral formulations. In this approach, the target freezing point depression (FPD) of body fluids (≈ 0.52°C) is matched by summing the ΔTf contributions of all solutes, then adding an isotonic agent (e.g., NaCl, dextrose, mannitol) to reach the desired value. Key concepts include colligative properties, van’t Hoff factor (i), cryoscopic constant of water (Kf = 1.86°C·kg·mol⁻¹), ΔTf additivity, NaCl equivalence, and handling multiple solutes and volumes. This method helps B. Pharm students make accurate, patient-safe tonicity adjustments for eye drops and injections using practical formulas and data. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the approximate freezing point depression (FPD) of isotonic body fluids such as blood and tears?

  • 0.52°C
  • 0.92°C
  • 0.58°C
  • 1.86°C

Correct Answer: 0.52°C

Q2. A 1% w/v NaCl solution produces an FPD of approximately:

  • 0.58°C
  • 0.52°C
  • 1.86°C
  • 0.18°C

Correct Answer: 0.58°C

Q3. Which equation underpins the freezing point method for isotonicity calculations?

  • ΔTf = i · Kf · m
  • Henderson–Hasselbalch equation
  • Raoult’s law for vapor pressure lowering (direct form)
  • Arrhenius equation

Correct Answer: ΔTf = i · Kf · m

Q4. Which is the correct sequence for the freezing point method in compounding?

  • Compute ΔTf of solutes → Subtract from 0.52°C → Convert remainder to % of isotonic agent → Adjust to final volume
  • Choose isotonic agent → Adjust to volume → Compute ΔTf → Subtract from 0.52°C
  • Compute E-values → Ignore ΔTf → Add NaCl → Adjust to volume
  • Measure pH → Add buffer → Adjust to volume → Add NaCl

Correct Answer: Compute ΔTf of solutes → Subtract from 0.52°C → Convert remainder to % of isotonic agent → Adjust to final volume

Q5. A 1% w/v solution of Drug X depresses the freezing point by 0.08°C. What concentration of Drug X alone would be isotonic?

  • 6.5% w/v
  • 5.2% w/v
  • 8.0% w/v
  • 4.16% w/v

Correct Answer: 6.5% w/v

Q6. Prepare 30 mL of a 2% w/v Drug Y eye drop. ΔTf per 1% Drug Y = 0.12°C. How much NaCl is required?

  • 0.145 g
  • 0.290 g
  • 0.060 g
  • 0.048 g

Correct Answer: 0.145 g

Q7. A formula has 1% Drug A (ΔTf/1% = 0.10°C) and 3% Drug B (ΔTf/1% = 0.05°C). What % w/v NaCl is needed to make it isotonic?

  • 0.47% w/v
  • 0.27% w/v
  • 0.58% w/v
  • 0.76% w/v

Correct Answer: 0.47% w/v

Q8. How many grams of NaCl are needed to make 50 mL isotonic if current ΔTf of solutes is 0.12°C?

  • 0.345 g
  • 0.230 g
  • 0.400 g
  • 0.690 g

Correct Answer: 0.345 g

Q9. A 0.9% w/v NaCl solution is isotonic because its expected ΔTf is closest to:

  • 0.52°C
  • 0.58°C
  • 0.90°C
  • 1.86°C

Correct Answer: 0.52°C

Q10. Which statement about isotonicity versus iso-osmotic solutions is TRUE?

  • Iso-osmotic solutions may not be isotonic if solutes permeate cell membranes
  • Iso-osmotic and isotonic are always identical
  • Isotonicity depends only on pH, not particle number
  • Freezing point method cannot distinguish tonicity differences

Correct Answer: Iso-osmotic solutions may not be isotonic if solutes permeate cell membranes

Q11. A key advantage of the freezing point method is that it:

  • Allows direct additivity of ΔTf values from multiple solutes toward the 0.52°C target
  • Eliminates the need to know final volume
  • Works without any data on solute properties
  • Requires activity coefficients for each solute

Correct Answer: Allows direct additivity of ΔTf values from multiple solutes toward the 0.52°C target

Q12. The cryoscopic constant (Kf) of water is approximately:

  • 1.86°C·kg·mol⁻¹
  • 0.52°C
  • 58.5 g·mol⁻¹
  • 273 K

Correct Answer: 1.86°C·kg·mol⁻¹

Q13. The van’t Hoff factor (i) for NaCl in dilute aqueous solution is approximately:

  • 1.8
  • 1.0
  • 2.0
  • 0.9

Correct Answer: 1.8

Q14. When using the freezing point method, ΔTf contributions from different solutes are:

  • Summed to obtain total ΔTf
  • Multiplied to obtain total ΔTf
  • Averaged to obtain total ΔTf
  • Ignored for electrolytes

Correct Answer: Summed to obtain total ΔTf

Q15. Which isotonicity-adjusting agent is preferred when sodium restriction is required?

  • Dextrose
  • Sodium bicarbonate
  • Sodium chloride
  • Sodium sulfate

Correct Answer: Dextrose

Q16. Why is boric acid acceptable for ophthalmic isotonicity adjustment but not for parenterals?

  • It is not isotonic with blood and can cause hemolysis
  • It is too volatile for injections
  • It has unacceptable taste
  • It raises pH above 10 in blood

Correct Answer: It is not isotonic with blood and can cause hemolysis

Q17. An ophthalmic solution has a total ΔTf of 0.60°C. It is best described as:

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

Correct Answer: Hypertonic

Q18. If ΔTf per 1% w/v of Drug Z is 0.14°C, what is the NaCl equivalent (E-value) per gram of Drug Z?

  • 0.24
  • 0.14
  • 0.58
  • 0.41

Correct Answer: 0.24

Q19. You need 15 mL of isotonic nasal drops with 0.5% w/v Drug Q (ΔTf/1% = 0.09°C). How much NaCl should be added?

  • 0.123 g
  • 0.082 g
  • 0.246 g
  • 0.475 g

Correct Answer: 0.123 g

Q20. For 100 mL containing 1% w/v mannitol (ΔTf/1% = 0.09°C), what % w/v dextrose (ΔTf/1% = 0.10°C) must be added to reach isotonicity?

  • 4.3% w/v
  • 0.43% w/v
  • 3.4% w/v
  • 5.8% w/v

Correct Answer: 4.3% w/v

Q21. Regarding compounding sequence for isotonic adjustment, which is correct?

  • Calculate grams of isotonic agent for the final volume, add it to dissolved solutes, then q.s. to volume
  • q.s. to volume first, then add the calculated isotonic agent
  • Add extra water after sterilization to compensate tonicity
  • Add isotonic agent based on initial wetting volume only

Correct Answer: Calculate grams of isotonic agent for the final volume, add it to dissolved solutes, then q.s. to volume

Q22. According to ΔTf = i·Kf·m, if solute molality doubles (dilute solution), the FPD will approximately:

  • Double
  • Halve
  • Remain unchanged
  • Increase fourfold

Correct Answer: Double

Q23. To compute NaCl needed by the freezing point method, you must know:

  • The ΔTf caused by the solute(s) at their intended concentrations
  • The pKa of each solute
  • The partition coefficient of active drug
  • The refractive index of the solvent

Correct Answer: The ΔTf caused by the solute(s) at their intended concentrations

Q24. In hypotonic solutions relative to blood, red blood cells tend to:

  • Hemolyze (swell and rupture)
  • Crenate (shrink)
  • Remain unchanged
  • Aggregate without volume change

Correct Answer: Hemolyze (swell and rupture)

Q25. Ophthalmic solutions are generally tolerated within which NaCl-equivalent tonicity range?

  • 0.6% to 2.0% w/v
  • 0.1% to 0.3% w/v
  • 2.5% to 5.0% w/v
  • Only exactly 0.9% w/v

Correct Answer: 0.6% to 2.0% w/v

Q26. Prepare 20 mL eye drops with Drug A 0.4 g; ΔTf/1% = 0.11°C. Buffer adds ΔTf = 0.06°C. How much NaCl is needed?

  • 0.083 g
  • 0.166 g
  • 0.041 g
  • 0.120 g

Correct Answer: 0.083 g

Q27. A negative NaCl requirement calculated via the freezing point method indicates:

  • The formulation is already hypertonic (requires dilution, not NaCl)
  • An arithmetic error always
  • The formulation is hypotonic
  • That more buffering salts are needed

Correct Answer: The formulation is already hypertonic (requires dilution, not NaCl)

Q28. For injectable preparations, the target ΔTf should be kept:

  • As close to 0.52°C as possible
  • Between 0.30°C and 0.80°C
  • At any value if sterile
  • Matched to tears (0.52°C ± 0.30°C)

Correct Answer: As close to 0.52°C as possible

Q29. A solution contains 4% Drug B (ΔTf/1% = 0.07°C) and 5% dextrose (ΔTf/1% = 0.10°C). What % w/v NaCl should be added?

  • 0% w/v (already hypertonic)
  • 0.43% w/v
  • 0.24% w/v
  • 0.10% w/v

Correct Answer: 0% w/v (already hypertonic)

Q30. Why is the freezing point method additive across solutes?

  • Because ΔTf is a colligative property dependent on total particle molality, so individual contributions sum in dilute solutions
  • Because solute volumes are strictly additive
  • Because all solutes have the same van’t Hoff factor
  • Because ΔTf depends only on solvent identity

Correct Answer: Because ΔTf is a colligative property dependent on total particle molality, so individual contributions sum in dilute solutions

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