Ideal solubility parameters MCQs With Answer

Ideal solubility parameters MCQs With Answer provide B. Pharm students a focused way to master solubility theory for drug design and formulation. This introduction covers key concepts such as Hildebrand and Hansen solubility parameters, cohesive energy density, Flory–Huggins interaction, and practical use in predicting drug–excipient compatibility, solvent selection, and miscibility of polymers and small molecules. Emphasis on units (MPa0.5), calculation methods, and limitations helps students apply theory to real pharmaceutical problems like solubilization, crystallization, and stability. These targeted MCQs will strengthen conceptual clarity and problem-solving skills for formulation development and regulatory dossiers. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What does the Hildebrand solubility parameter (δ) primarily quantify?

• The energy required to ionize a molecule
• The square root of cohesive energy density
• The dielectric constant of a solvent
• The pH at which a drug is soluble

Correct Answer: The square root of cohesive energy density

Q2. Which formula represents the Hildebrand solubility parameter?

• δ = √(ΔHvap/Vm)
• δ = ΔGfus / Tm
• δ = √(CED) where CED = ΔEvap/Vm
• δ = ln x2 = -ΔHf/R(1/T – 1/Tm)

Correct Answer: δ = √(CED) where CED = ΔEvap/Vm

Q3. What are the three components of the Hansen solubility parameter?

• Dispersion, polar, and hydrogen-bonding
• Viscosity, density, and refractive index
• Acidic, basic, and neutral
• Enthalpy, entropy, and free energy

Correct Answer: Dispersion, polar, and hydrogen-bonding

Q4. In which units are solubility parameters commonly expressed?

• g·cm−3
• MPa0.5 or (cal·cm−3)0.5
• mol·L−1
• J·K−1·mol−1

Correct Answer: MPa0.5 or (cal·cm−3)0.5

Q5. Which statement best describes “like dissolves like” in terms of solubility parameters?

• Substances with similar δ values are more likely to be miscible
• Substances with very different δ values form stable solutions
• Only polar solvents dissolve polar solutes regardless of δ
• Hydrophobic drugs always require surfactants

Correct Answer: Substances with similar δ values are more likely to be miscible

Q6. How is the Hansen distance (Ra) between two materials calculated qualitatively?

• Ra = difference in boiling points
• Ra = √[4(Δδd)^2 + (Δδp)^2 + (Δδh)^2]
• Ra = sum of molecular weights
• Ra = ΔpKa × ΔlogP

Correct Answer: Ra = √[4(Δδd)^2 + (Δδp)^2 + (Δδh)^2]

Q7. What is the main limitation of the Hildebrand solubility parameter?

• It cannot be calculated from experimental data
• It ignores specific interactions like hydrogen bonding and polar interactions
• It is only valid for ionic compounds
• It is too complex for practical use

Correct Answer: It ignores specific interactions like hydrogen bonding and polar interactions

Q8. Which of the following best defines cohesive energy density (CED)?

• CED = viscosity × molar volume
• CED = molar mass / density
• CED = energy of vaporization per unit molar volume
• CED = dielectric constant squared

Correct Answer: CED = energy of vaporization per unit molar volume

Q9. Which equation gives the ideal mole fraction solubility of a solid in a liquid, neglecting activity coefficients?

• x = P°/P
• ln x = -ΔHf/R (1/T – 1/Tm)
• x = δsolute/δsolvent
• χ = RT/(Vref(δ1-δ2)^2)

Correct Answer: ln x = -ΔHf/R (1/T – 1/Tm)

Q10. In the ideal solubility equation ln x = -ΔHf/R(1/T – 1/Tm), what does ΔHf represent?

• Heat of fusion (enthalpy of melting)
• Heat of vaporization
• Heat capacity at constant pressure
• Activation energy for dissolution

Correct Answer: Heat of fusion (enthalpy of melting)

Q11. Why are Hansen parameters preferred over Hildebrand for polar and hydrogen-bonding systems?

• They require fewer experimental data
• They separate dispersion, polar, and hydrogen-bonding contributions
• They only apply to gases
• They use molecular weight instead of energy terms

Correct Answer: They separate dispersion, polar, and hydrogen-bonding contributions

Q12. For polymer-solvent compatibility, a small difference in solubility parameter indicates:

• Low miscibility and phase separation
• High miscibility and good solvent quality
• Polymer degradation
• Increase in glass transition temperature

Correct Answer: High miscibility and good solvent quality

Q13. What does a large Hansen distance Ra between drug and excipient imply?

• Higher likelihood of miscibility
• Lower chance of miscibility and possible phase separation
• Increased dissolution rate
• Enhanced hydrogen bonding

Correct Answer: Lower chance of miscibility and possible phase separation

Q14. The Flory–Huggins interaction parameter χ is often related to solubility parameters by which expression (qualitative)?

• χ ≈ Vref(δ1 – δ2)^2 / RT
• χ = ln γ
• χ = ΔHf/ΔS
• χ = 1/(δ1 + δ2)

Correct Answer: χ ≈ Vref(δ1 – δ2)^2 / RT

Q15. Which practical use of solubility parameters is most relevant to B. Pharm formulation scientists?

• Predicting solvent toxicity
• Choosing compatible excipients to prevent drug crystallization
• Measuring tablet hardness directly
• Estimating pKa of acidic drugs

Correct Answer: Choosing compatible excipients to prevent drug crystallization

Q16. Which value of Δδ (difference between solubility parameters) generally indicates good compatibility for small molecules?

• Very large (>10 MPa0.5)
• Moderate (~5–10 MPa0.5)
• Small (<2 MPa0.5)
• Negative values only

Correct Answer: Small (<2 MPa0.5)

Q17. What experimental data can be used to estimate the Hildebrand parameter of a liquid?

• Molar volume and heat of vaporization
• Viscosity and refractive index
• Boiling point and pH
• Melting point and density only

Correct Answer: Molar volume and heat of vaporization

Q18. Which of the following is an assumption of the ideal solubility model for solids in liquids?

• There are strong specific interactions between solute and solvent
• Activity coefficients equal unity (ideal behavior)
• Solute completely ionizes in solvent
• The solvent is a supercritical fluid

Correct Answer: Activity coefficients equal unity (ideal behavior)

Q19. Why is temperature important in solubility parameter calculations?

• Solubility parameters are independent of temperature
• CED and vaporization energy change with temperature, altering δ
• Only solvent polarity changes with temperature
• Phase diagrams collapse at higher temperature

Correct Answer: CED and vaporization energy change with temperature, altering δ

Q20. Which of these techniques can be used experimentally to determine solubility parameter by matching solubility behavior?

• Solubility sphere/Hansen solubility testing using multiple solvents
• Mass spectrometry of solvent mixture
• IR spectroscopy alone
• Microscopy of crystals only

Correct Answer: Solubility sphere/Hansen solubility testing using multiple solvents

Q21. If a drug has δ = 20 MPa0.5 and solvent has δ = 22 MPa0.5, what can be inferred?

• They are likely immiscible
• They have moderate compatibility and may be miscible depending on specific interactions
• The drug will ionize in the solvent
• They will react chemically

Correct Answer: They have moderate compatibility and may be miscible depending on specific interactions

Q22. How does polymer molecular weight affect miscibility where solubility parameters are similar?

• Higher molecular weight always increases miscibility
• Higher molecular weight can reduce miscibility due to entropy penalty
• Molecular weight has no effect
• Only crosslinking matters

Correct Answer: Higher molecular weight can reduce miscibility due to entropy penalty

Q23. Which parameter is most useful to predict crystallization tendency in amorphous solid dispersions?

• Hansen solubility parameter difference between drug and polymer
• Boiling point of polymer
• Optical rotation
• Ionization constant

Correct Answer: Hansen solubility parameter difference between drug and polymer

Q24. What does a negative Flory–Huggins χ value indicate for polymer–solvent interactions?

• Repulsive interactions and immiscibility
• Attractive interactions and enhanced miscibility
• Polymer degradation
• Solvent evaporation

Correct Answer: Attractive interactions and enhanced miscibility

Q25. Which of these is NOT a component in calculating Hansen solubility parameter distance?

• Dispersion component difference (Δδd)
• Pressure difference (ΔP)
• Polar component difference (Δδp)
• Hydrogen-bonding component difference (Δδh)

Correct Answer: Pressure difference (ΔP)

Q26. For ionic drugs, why are classical solubility parameters sometimes insufficient?

• Ionic interactions and solvation are dominated by electrostatics not captured by δ
• Ionic drugs have zero cohesive energy
• The Hildebrand parameter is undefined for ions
• Ionic drugs always have higher melting points

Correct Answer: Ionic interactions and solvation are dominated by electrostatics not captured by δ

Q27. Which statement about Raoult’s law and ideal solutions is correct?

• Raoult’s law applies only to nonvolatile solutes
• Raoult’s law relates partial vapor pressure to mole fraction for ideal solutions
• Raoult’s law predicts solubility without enthalpy data
• Raoult’s law is used to compute Hansen parameters

Correct Answer: Raoult’s law relates partial vapor pressure to mole fraction for ideal solutions

Q28. Which of the following increases the ideal solubility of a crystalline drug at a given temperature?

• Higher heat of fusion (ΔHf)
• Lower melting point (Tm)
• Lower temperature (T)
• Higher crystal lattice energy

Correct Answer: Lower melting point (Tm)

Q29. In practice, why might experimentally measured solubility deviate from ideal solubility predicted by ln x = -ΔHf/R(1/T – 1/Tm)?

• Because ideal model ignores non-ideal activity coefficients and specific interactions
• Because ΔHf is temperature-independent
• Because ideal solubility always matches experimental values
• Because we cannot measure Tm accurately

Correct Answer: Because ideal model ignores non-ideal activity coefficients and specific interactions

Q30. Which property of a solvent would most directly lower the Hansen polar component δp?

• Increasing solvent dipole moment
• Decreasing solvent dipole moment (less polarity)
• Adding hydrogen-bond donors
• Raising solvent boiling point

Correct Answer: Decreasing solvent dipole moment (less polarity)

Q31. When selecting a co-solvent for a poorly soluble drug, how are solubility parameters used?

• Choose a co-solvent with a very different δ to induce phase separation
• Choose a co-solvent with a δ close to the drug to improve solubility
• Only viscosity matters for co-solvent choice
• Co-solvent selection ignores δ values

Correct Answer: Choose a co-solvent with a δ close to the drug to improve solubility

Q32. The Hildebrand parameter cannot distinguish which of the following interactions?

• London dispersion forces
• Specific hydrogen bonding interactions
• Van der Waals interactions
• Cohesive energy contributions

Correct Answer: Specific hydrogen bonding interactions

Q33. For a drug–polymer system, matching which Hansen component is most critical to inhibit recrystallization for hydrogen-bonding drugs?

• Dispersion component δd only
• Polar component δp only
• Hydrogen-bonding component δh
• Melting point similarity

Correct Answer: Hydrogen-bonding component δh

Q34. Which calculation approach can estimate solubility parameters from molecular groups?

• Group contribution methods (e.g., Hoy or Van Krevelen)
• Direct X-ray crystallography
• HPLC retention time only
• pKa titration curves

Correct Answer: Group contribution methods (e.g., Hoy or Van Krevelen)

Q35. If polymer and drug are within the same Hansen solubility sphere, what does it imply?

• They are likely incompatible
• They are likely compatible and soluble in each other
• The polymer will crystallize the drug
• They will react chemically

Correct Answer: They are likely compatible and soluble in each other

Q36. Which of the following is a consequence of ignoring specific interactions in formulation design?

• Perfect prediction of long-term stability
• Potential failure of selected excipient due to phase separation or recrystallization
• Guaranteed improved bioavailability
• Polymer molecular weight becomes irrelevant

Correct Answer: Potential failure of selected excipient due to phase separation or recrystallization

Q37. How does plasticization of a polymer by a solvent relate to solubility parameters?

• A solvent with δ far from polymer δ will plasticize it best
• A solvent with δ similar to polymer δ is more likely to swell and plasticize the polymer
• Plasticization only depends on temperature
• Plasticization cannot be predicted by δ

Correct Answer: A solvent with δ similar to polymer δ is more likely to swell and plasticize the polymer

Q38. Which method helps visualize Hansen solubility parameter relationships among solvents and solutes?

• Hansen solubility sphere plotted in 3D space (δd, δp, δh)
• NMR spectroscopy alone
• pKa vs logP graph
• DSC melting point scan only

Correct Answer: Hansen solubility sphere plotted in 3D space (δd, δp, δh)

Q39. What is a practical threshold often used for approximate miscibility using Hildebrand δ difference for polymers?

• Δδ > 10 MPa0.5 indicates miscibility
• Δδ ≈ 0–2 MPa0.5 suggests likely miscibility
• Δδ must be negative for miscibility
• Any Δδ value is irrelevant for polymers

Correct Answer: Δδ ≈ 0–2 MPa0.5 suggests likely miscibility

Q40. Which experimental observation would suggest non-ideal behavior in a drug–solvent system?

• Measured solubility equals ideal solubility prediction
• Significant deviation between measured and ideal solubility, indicating activity coefficient ≠ 1
• Boiling point of solvent decreases with addition of drug
• Color change only with no solubility change

Correct Answer: Significant deviation between measured and ideal solubility, indicating activity coefficient ≠ 1

Q41. Which of the following improves the predictive power of solubility parameters for pharmaceutical systems?

• Combining Hansen parameters with experimental solubility screening and thermodynamic models
• Using Hildebrand parameter alone for all systems
• Ignoring temperature effects
• Only using pKa values

Correct Answer: Combining Hansen parameters with experimental solubility screening and thermodynamic models

Q42. When calculating δ from vaporization data, which volume should be used?

• Molar volume of the substance
• Volume of 1 mL
• Density at 0°C only
• Polymer free volume exclusively

Correct Answer: Molar volume of the substance

Q43. Which effect can hydrogen bonding between drug and polymer have on physical stability of an amorphous dispersion?

• Promote phase separation
• Enhance physical stability and inhibit recrystallization
• Always cause chemical degradation
• Reduce molecular weight

Correct Answer: Enhance physical stability and inhibit recrystallization

Q44. Which parameter would you examine to assess solvent potency for extraction of a lipophilic drug?

• Solubility parameter close to that of the lipophilic drug
• Only solvent boiling point
• Solvent pKa
• Solvent flash point only

Correct Answer: Solubility parameter close to that of the lipophilic drug

Q45. Which of the following is a correct statement about group contribution methods for δ?

• They provide approximate δ values using contributions from chemical functional groups
• They require full experimental vaporization data for each compound
• They are useless for polymers
• They always give exact δ values

Correct Answer: They provide approximate δ values using contributions from chemical functional groups

Q46. What practical step should a formulator take if the calculated δ difference suggests poor miscibility?

• Proceed without further testing
• Screen alternative excipients or use surfactants/co-solvents and perform experimental solubility tests
• Increase the manufacturing temperature indefinitely
• Always choose a solvent with higher δ

Correct Answer: Screen alternative excipients or use surfactants/co-solvents and perform experimental solubility tests

Q47. Which is TRUE about the solvent power of water in terms of solubility parameters?

• Water has low δh and is nonpolar
• Water has high polar and hydrogen-bonding components, making it a strong hydrogen-bonding solvent
• Water’s δd is the sole determinant of its solvent power
• Water acts like a nonpolar organic solvent

Correct Answer: Water has high polar and hydrogen-bonding components, making it a strong hydrogen-bonding solvent

Q48. Which of the following can reduce the ideal solubility of a drug in a solvent?

• Decreasing ΔHf
• Raising the temperature close to Tm
• Increasing crystal lattice energy or increasing ΔHf
• Using a solvent with identical δ

Correct Answer: Increasing crystal lattice energy or increasing ΔHf

Q49. For dosage form development, why is understanding solubility parameters important for scale-up and manufacturing?

• They help predict long-term tablet color changes
• They assist in choosing solvents and excipients that maintain stability and processability during scale-up
• They define the exact dissolution profile without testing
• They eliminate need for stability studies

Correct Answer: They assist in choosing solvents and excipients that maintain stability and processability during scale-up

Q50. Which combined strategy yields the most reliable prediction of drug–excipient compatibility?

• Relying solely on Hildebrand δ values
• Combining Hansen parameters, experimental solubility testing, and thermodynamic models like Flory–Huggins
• Using pKa and melting point only
• Guessing based on similar chemical names

Correct Answer: Combining Hansen parameters, experimental solubility testing, and thermodynamic models like Flory–Huggins

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