Theoretical approaches for determining physicochemical parameters MCQs With Answer

Theoretical approaches for determining physicochemical parameters are essential for B. Pharm students to predict drug behavior during formulation and development. This introduction covers key concepts—partition coefficient (logP), distribution coefficient (logD), pKa, solubility, lipophilicity, Hansen solubility parameters, dielectric effects, and in silico prediction methods—along with experimental approaches like shake-flask, potentiometric titration, spectrophotometric, HPLC-based, and computational QSAR models. Understanding factors such as temperature, ionic strength, polymorphism, and micellar solubilization improves interpretation of results and method selection. Mastery of these theoretical and practical tools aids rational excipient choice, bioavailability assessment, and regulatory compliance. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which parameter primarily quantifies a compound’s equilibrium preference between octanol and water?

• Partition coefficient (logP)
• pKa value
• Dielectric constant
• Viscosity

Correct Answer: Partition coefficient (logP)

Q2. Which method is considered the classical experimental technique for determining logP?

• Shake-flask method
• Potentiometric titration
• Capillary electrophoresis
• PAMPA assay

Correct Answer: Shake-flask method

Q3. Distribution coefficient (logD) differs from logP by accounting for which factor?

• Ionization state at a specific pH
• Temperature dependence
• Surface tension of phases
• Polymorphic form of the solid

Correct Answer: Ionization state at a specific pH

Q4. Which theoretical approach estimates solubility based on cohesive energy and dispersion forces?

• Hansen solubility parameters
• Henderson-Hasselbalch equation
• Shake-flask experiment
• PAMPA model

Correct Answer: Hansen solubility parameters

Q5. For weak acids and bases, which equation is central to predict pH-dependent solubility and ionization?

• Henderson-Hasselbalch equation
• Arrhenius equation
• Van ‘t Hoff equation
• Michaelis-Menten equation

Correct Answer: Henderson-Hasselbalch equation

Q6. Which measurement technique is most suitable for determining pKa by observing absorbance changes with pH?

• UV-visible spectrophotometric titration
• Shake-flask partitioning
• NMR relaxation time
• Dynamic light scattering

Correct Answer: UV-visible spectrophotometric titration

Q7. In potentiometric pKa determination, what is directly measured?

• pH as a function of added titrant
• Partitioning into octanol
• Dielectric constant of solvent
• Viscosity of solution

Correct Answer: pH as a function of added titrant

Q8. Which computational method predicts physicochemical parameters from molecular structure using statistical models?

• QSAR/QSPR models
• Shake-flask experimental method
• Potentiometric titration
• Hansen parameter mixing

Correct Answer: QSAR/QSPR models

Q9. Which factor most strongly affects partitioning into biological membranes and permeability?

• Lipophilicity (logP/logD)
• Dielectric constant of octanol
• Refractive index of water
• Glass transition temperature

Correct Answer: Lipophilicity (logP/logD)

Q10. Which experimental approach can determine logP for ionizable drugs across pH range automatically?

• Potentiometric logP/logD titration
• Standard shake-flask at single pH
• Melting point analysis
• Diffusion cell permeability

Correct Answer: Potentiometric logP/logD titration

Q11. What is the main limitation of the shake-flask method for highly lipophilic compounds?

• Very low aqueous concentrations leading to detection limits
• Rapid chemical degradation in octanol
• Incompatibility with pH measurement
• Requirement for radioactive labeling

Correct Answer: Very low aqueous concentrations leading to detection limits

Q12. Which spectroscopic technique can be used to determine diffusion coefficients theoretically and experimentally?

• NMR (pulsed field gradient)
• Infrared absorbance
• Fluorescence lifetime only
• UV-visible in static mode

Correct Answer: NMR (pulsed field gradient)

Q13. Hansen solubility parameters separate cohesive energy into which three components?

• Dispersion, polar, hydrogen-bonding
• Dielectric, refractive, viscosity
• Acidic, basic, neutral
• Hydrophobic, hydrophilic, amphiphilic

Correct Answer: Dispersion, polar, hydrogen-bonding

Q14. Which property is directly influenced by polymorphism in solid drugs?

• Solubility and dissolution rate
• Octanol dielectric constant
• PKa in aqueous solution
• Color in octanol phase

Correct Answer: Solubility and dissolution rate

Q15. The Henderson-Hasselbalch equation helps calculate the fraction of drug ionized at a given pH. For a weak base, if pH < pKa, the base is predominantly:

• Protonated (ionized)
• Neutral (unionized)
• Precipitated
• Degraded

Correct Answer: Protonated (ionized)

Q16. Which parameter describes how solute concentration deviates from ideal behavior due to interactions?

• Activity coefficient
• Partition coefficient
• Dielectric increment
• LogS value

Correct Answer: Activity coefficient

Q17. Which HPLC-based approach can be used to estimate lipophilicity rapidly?

• Log k (retention factor) correlation with logP
• Direct pKa titration on-column
• Measuring mobile phase viscosity
• Solid-state NMR of stationary phase

Correct Answer: Log k (retention factor) correlation with logP

Q18. Which theoretical relation describes temperature dependence of solubility via enthalpy change?

• van ‘t Hoff equation
• Henderson-Hasselbalch equation
• Stokes-Einstein equation
• Hansen mixing rule

Correct Answer: van ‘t Hoff equation

Q19. Micellar solubilization affects apparent solubility by which mechanism?

• Incorporation of hydrophobic drug into micelle cores
• Changing drug’s pKa permanently
• Converting drug into crystalline form
• Increasing dielectric constant of octanol

Correct Answer: Incorporation of hydrophobic drug into micelle cores

Q20. Which in silico tool type predicts pKa and logP from molecular structure using fragment contributions?

• Empirical fragment-based calculators (e.g., ACD/Percepta)
• Shake-flask simulators
• PFG-NMR simulators
• HPLC retentivity databases only

Correct Answer: Empirical fragment-based calculators (e.g., ACD/Percepta)

Q21. Which experimental complication can bias logD measurements in octanol–water systems?

• Octanol/water mutual solubility and water content in octanol
• Mismatch of pipette tips
• UV detector wavelength drift
• Column packing density

Correct Answer: Octanol/water mutual solubility and water content in octanol

Q22. Which theoretical concept links molecular size and solvent viscosity to diffusion coefficient?

• Stokes-Einstein equation
• Henderson-Hasselbalch equation
• van ‘t Hoff relation
• Hansen solubility theory

Correct Answer: Stokes-Einstein equation

Q23. Capillary electrophoresis can be used to estimate pKa by observing:

• Mobility shifts with pH
• Octanol partitioning directly
• Thermal transitions of the solid
• Micelle formation in octanol

Correct Answer: Mobility shifts with pH

Q24. Which parameter is most useful to predict oral absorption when combined with solubility?

• Permeability (e.g., PAMPA or Caco-2 data)
• Melting point alone
• Viscosity of formulation
• Dielectric constant of octanol

Correct Answer: Permeability (e.g., PAMPA or Caco-2 data)

Q25. Which of the following is a limitation of purely theoretical QSAR predictions for physicochemical properties?

• May not capture solid-state effects like polymorphism
• Always more accurate than experiments
• Requires radiolabeled compounds
• Cannot predict logP at all

Correct Answer: May not capture solid-state effects like polymorphism

Q26. Zeta potential measurement primarily informs about:

• Colloidal stability and surface charge of particles
• Octanol-water partitioning of neutral molecules
• Absolute pKa values of neutral drugs
• Hansen hydrogen-bonding parameter only

Correct Answer: Colloidal stability and surface charge of particles

Q27. When estimating aqueous solubility from melting point and lipophilicity, which rule is commonly referenced?

• General solubility equation (GSE)
• Henderson-Hasselbalch rule
• van ‘t Hoff partition theorem
• Stokes-Einstein liberation rule

Correct Answer: General solubility equation (GSE)

Q28. Which experimental measurement helps distinguish between true solubility and colloidal-solubilized drug?

• Filtration/centrifugation followed by analysis of dissolved fraction
• Measuring refractive index of octanol
• Direct potentiometric pKa only
• Visual color comparison

Correct Answer: Filtration/centrifugation followed by analysis of dissolved fraction

Q29. Dielectric constant of a medium primarily affects which interaction relevant to solubility and ionization?

• Electrostatic interactions between charged species
• Dispersion forces only
• Lattice energy of crystalline octanol
• Hydrogen bonding in vacuum

Correct Answer: Electrostatic interactions between charged species

Q30. Which combined approach gives the most reliable assessment of a drug’s physicochemical profile?

• Integrating experimental methods (shake-flask, potentiometry, HPLC) with in silico predictions
• Only in silico prediction without any experiments
• Only melting point measurement
• Measuring color and odor of solid drug

Correct Answer: Integrating experimental methods (shake-flask, potentiometry, HPLC) with in silico predictions

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