Introduction: Understanding the limitations of distribution law is essential for B.Pharm students studying partitioning, solubility and drug distribution. The Nernst distribution law (partition law) predicts a constant concentration ratio of a solute between two immiscible solvents at equilibrium, but real-world factors — ionization, association, complexation, micellization, solvent interactions and temperature — often cause deviations. Recognizing these limitations helps in interpreting partition coefficient (log P) and distribution coefficient (log D) data, optimizing formulations, and predicting absorption, bioavailability and drug–solvent behavior. This concise guide focuses on practical implications and experimental pitfalls B.Pharm students must master. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What is the basic statement of the Nernst distribution law?
- The ratio of activities of a solute between two phases is variable with concentration
- At equilibrium, the ratio of concentrations of a solute in two immiscible solvents is constant if the solute exists in the same molecular form in both solvents
- The solute distributes equally by mass between two solvents regardless of solubility
- The partition coefficient is independent of temperature and ionic strength
Correct Answer: At equilibrium, the ratio of concentrations of a solute in two immiscible solvents is constant if the solute exists in the same molecular form in both solvents
Q2. Which of the following is a primary assumption of the distribution law?
- The solute undergoes ionization in one of the solvents
- The solute exists in different molecular forms in the two phases
- The solution is dilute and the solute remains chemically identical in both phases
- The temperature must be above boiling point of one solvent
Correct Answer: The solution is dilute and the solute remains chemically identical in both phases
Q3. Which factor commonly causes deviation from the distribution law?
- Presence of the same molecular form in both phases
- Ionization of the solute in one phase
- Very low solute concentration under ideal conditions
- Strictly immiscible solvents
Correct Answer: Ionization of the solute in one phase
Q4. When a solute forms an ion in aqueous phase but remains unionized in organic phase, the distribution law fails because:
- The unionized species is absent
- Different molecular forms exist in the two phases
- The solvents become miscible
- The solute concentration is too high
Correct Answer: Different molecular forms exist in the two phases
Q5. The distribution coefficient (D) differs from partition coefficient (P) because:
- D includes all molecular species of the solute in a phase at a given pH, while P refers to a single un-ionized species
- P accounts for ionized and unionized forms, D only for unionized
- They are identical under all conditions
- D is independent of pH but P is pH dependent
Correct Answer: D includes all molecular species of the solute in a phase at a given pH, while P refers to a single un-ionized species
Q6. Which experimental method is most commonly used to determine partition coefficient by distribution law?
- Ultracentrifugation
- Shake-flask method
- Gas chromatography without phase separation
- Mass spectrometry in vacuum
Correct Answer: Shake-flask method
Q7. How does association (dimerization) of a solute affect the distribution law?
- It has no effect because association occurs equally in both phases
- Association alters the apparent concentration, causing deviations from the constant ratio
- It always increases the partition coefficient proportionally
- Association only affects volatile solutes
Correct Answer: Association alters the apparent concentration, causing deviations from the constant ratio
Q8. Which of these causes is related to solvent-solute interactions modifying distribution behavior?
- Complex formation with solvent molecules (solvation)
- Complete immiscibility of solvents
- Strict dilution of solute
- Constant temperature
Correct Answer: Complex formation with solvent molecules (solvation)
Q9. Why does temperature influence the applicability of the distribution law?
- Temperature changes always make solvents miscible
- Temperature can change solute solubility, association constants and equilibrium, altering partition ratio
- Distribution law assumes high temperatures only
- Temperature only affects gaseous solutes
Correct Answer: Temperature can change solute solubility, association constants and equilibrium, altering partition ratio
Q10. In presence of surfactants above CMC, distribution experiments may fail due to:
- Increased ionic strength only
- Solute incorporation into micelles altering apparent distribution
- Complete removal of organic solvent
- Lowering of temperature
Correct Answer: Solute incorporation into micelles altering apparent distribution
Q11. How does complexation with other solutes affect Nernst distribution law?
- Complexation reduces deviations and enforces constant ratio
- Complexation produces new species, invalidating the single-species assumption of the law
- Complexation only affects solid-state distribution
- Complexation speeds up equilibrium without altering ratios
Correct Answer: Complexation produces new species, invalidating the single-species assumption of the law
Q12. Which statement is true regarding ionic strength and distribution measurements?
- Ionic strength never affects ionized drug distribution
- Changes in ionic strength can alter ionization equilibria and activity coefficients, affecting distribution
- Ionic strength only affects organic solvents
- Distribution coefficients are corrected automatically for ionic strength
Correct Answer: Changes in ionic strength can alter ionization equilibria and activity coefficients, affecting distribution
Q13. What is a corrective approach when a drug ionizes and distribution law fails?
- Ignore ionization and report P value
- Use distribution coefficient (D) at a defined pH or apply Henderson-Hasselbalch to calculate species fractions
- Always use pure water as solvent
- Raise temperature to force unionization
Correct Answer: Use distribution coefficient (D) at a defined pH or apply Henderson-Hasselbalch to calculate species fractions
Q14. The pH-partition hypothesis relates to distribution law by explaining:
- How pH affects solvent viscosity
- How ionization state of a drug affects its ability to cross membranes and distribute between aqueous and lipid phases
- Why partitioning is independent of pH
- How pH only affects solid dosage forms
Correct Answer: How ionization state of a drug affects its ability to cross membranes and distribute between aqueous and lipid phases
Q15. Which of these is an experimental pitfall when measuring distribution coefficient?
- Ensuring complete phase separation after equilibration
- Using extremely low solute concentrations only
- Ignoring emulsification and not centrifuging the mixture
- Working at room temperature
Correct Answer: Ignoring emulsification and not centrifuging the mixture
Q16. How does stereoisomerism affect partitioning and the distribution law?
- Stereoisomers always have identical partition behavior
- Differing stereoisomers can have different solvation and interactions, giving different partition ratios
- Stereoisomerism only impacts volatile compounds
- The distribution law accounts for stereochemistry inherently
Correct Answer: Differing stereoisomers can have different solvation and interactions, giving different partition ratios
Q17. If a drug associates to form aggregates in one phase, measured partition coefficient will likely be:
- Unaffected because aggregates are invisible
- Misleadingly low for monomer concentration in that phase
- Always higher than true monomer partition
- Exactly equal to theoretical P
Correct Answer: Misleadingly low for monomer concentration in that phase
Q18. Which term best describes the effective measure that includes both ionized and unionized species at a given pH?
- Log P
- Partition coefficient
- Distribution coefficient (log D)
- Solubility constant
Correct Answer: Distribution coefficient (log D)
Q19. In biological systems, which additional limitation reduces applicability of simple distribution law results?
- Negligible protein binding
- Plasma protein binding and tissue binding alter free drug concentration versus total concentration
- Equilibrium is always instantaneous in vivo
- Only unionized drug is present in plasma
Correct Answer: Plasma protein binding and tissue binding alter free drug concentration versus total concentration
Q20. When the solute undergoes chemical reaction in one phase, Nernst distribution law:
- Remains valid without modification
- Fails because the chemical identity of the solute changes in that phase
- Applies only if reaction is reversible
- Is improved because reaction speeds equilibrium
Correct Answer: Fails because the chemical identity of the solute changes in that phase
Q21. Why is the distribution law not applicable to electrolytes that fully dissociate in water?
- Because dissociation produces new ionic species with different affinities, violating single-species assumption
- Because electrolytes are always insoluble in organic solvents
- Because dissociation makes solvents miscible
- Because distribution law applies only to solids
Correct Answer: Because dissociation produces new ionic species with different affinities, violating single-species assumption
Q22. Which of the following best explains why co-solvents (like ethanol) can change measured partitioning?
- Co-solvents reduce vapor pressure only
- Co-solvents alter solvent polarity and solvation, changing solute distribution between phases
- Co-solvents uniformly decrease solute concentration in both phases
- Co-solvents increase the solute molecular weight
Correct Answer: Co-solvents alter solvent polarity and solvation, changing solute distribution between phases
Q23. In multi-compartment pharmacokinetic models, why is a single partition coefficient insufficient to predict distribution?
- Because biological tissues have different affinities, perfusion rates and binding sites producing multi-exponential distribution
- Because partition coefficients never vary between tissues
- Because drugs never equilibrate between compartments
- Because partitioning is irrelevant in vivo
Correct Answer: Because biological tissues have different affinities, perfusion rates and binding sites producing multi-exponential distribution
Q24. What is the effect of pKa on distribution of a weak acid between octanol and water?
- pKa is irrelevant to distribution
- pKa determines the fraction ionized at given pH, affecting how much remains unionized and partitions into octanol
- Higher pKa always means higher partition into octanol regardless of pH
- Lower pKa prevents any partitioning
Correct Answer: pKa determines the fraction ionized at given pH, affecting how much remains unionized and partitions into octanol
Q25. Which scenario best exemplifies solute-solvent complexation causing distribution law deviation?
- Weak van der Waals interactions only
- Formation of a stable hydrogen-bonded complex with water that does not exist in organic phase
- Identical solvation in both solvents
- Low temperature stabilizing both phases equally
Correct Answer: Formation of a stable hydrogen-bonded complex with water that does not exist in organic phase
Q26. In measuring log P for an amphoteric drug, what complication arises?
- Amphoteric drugs never distribute into organic phases
- They may exist as zwitterions or multiple ionic forms; distribution depends on pH and form present
- Amphoteric nature simplifies measurement
- Log P equals log D for amphoteric drugs at all pH
Correct Answer: They may exist as zwitterions or multiple ionic forms; distribution depends on pH and form present
Q27. How does adsorption to container walls produce apparent deviation from distribution law?
- Adsorption removes solute from measurable phase, changing apparent concentrations and ratio
- Adsorption always increases apparent concentration in both phases
- Adsorption only occurs with glass containers at high pH
- Adsorption is negligible and never affects partitioning
Correct Answer: Adsorption removes solute from measurable phase, changing apparent concentrations and ratio
Q28. Why is achieving true equilibrium important for distribution experiments?
- Because distribution law applies only at equilibrium; kinetic limitations cause false partition ratios
- Equilibrium is unnecessary if concentrations are low
- Distribution law refers to initial concentrations only
- Equilibrium speeds phase separation only
Correct Answer: Because distribution law applies only at equilibrium; kinetic limitations cause false partition ratios
Q29. Which parameter is most directly used to predict membrane permeability from partitioning data?
- Log P or log D values as indicators of lipophilicity and membrane affinity
- Molecular weight only
- Boiling point of solvent
- Solubility in salt solutions
Correct Answer: Log P or log D values as indicators of lipophilicity and membrane affinity
Q30. What is the likely effect on distribution if a drug forms a stable chelate with metal ions present in one phase?
- No effect because chelation is reversible
- Chelation creates a new species with different solubility, causing deviation from the original distribution law
- Chelation equalizes concentrations across phases
- Chelation only affects color, not distribution
Correct Answer: Chelation creates a new species with different solubility, causing deviation from the original distribution law
Q31. Which approach helps to obtain meaningful partition data for ionizable drugs?
- Measure partitioning at a single arbitrary pH
- Measure log P for unionized form (if possible) and log D across physiologically relevant pH values
- Always measure at pH 7.0 without adjustment
- Avoid measuring partitioning altogether
Correct Answer: Measure log P for unionized form (if possible) and log D across physiologically relevant pH values
Q32. In washout experiments, what does a changing partition ratio over time suggest?
- That equilibrium has been reached instantaneously
- Possible slow kinetics, adsorption, degradation or formation of new species affecting equilibrium
- That the distribution law holds perfectly
- That solvent densities are identical
Correct Answer: Possible slow kinetics, adsorption, degradation or formation of new species affecting equilibrium
Q33. Why is the Nernst distribution law not directly applicable to colloidal systems?
- Because colloids are solids
- Colloids involve micelles, emulsions or particles that solubilize solute differently than true molecular solutions, violating single-molecule distribution assumptions
- Colloids always obey the law better than molecular solutions
- Because colloids are always nonpolar
Correct Answer: Colloids involve micelles, emulsions or particles that solubilize solute differently than true molecular solutions, violating single-molecule distribution assumptions
Q34. How does hydrogen bonding ability of a solute influence its partitioning?
- Greater hydrogen bonding with water increases aqueous solubility and reduces partition into nonpolar phase
- Hydrogen bonding always increases partitioning into octanol
- Hydrogen bonding has no effect on distribution
- H-bonding decreases solubility in both phases equally
Correct Answer: Greater hydrogen bonding with water increases aqueous solubility and reduces partition into nonpolar phase
Q35. Which practical step can reduce experimental deviations when determining partition coefficients?
- Neglecting phase equilibration time
- Using proper phase separation techniques (centrifugation), controlling pH and ionic strength, and avoiding emulsions
- Not controlling temperature
- Using reactive containers that bind solute
Correct Answer: Using proper phase separation techniques (centrifugation), controlling pH and ionic strength, and avoiding emulsions
Q36. In the presence of co-solutes that compete for the organic phase, distribution law deviations occur because:
- Competitor co-solutes have no effect on distribution
- Competition changes phase composition and available space for solute solvation, altering apparent partitioning
- Competition only affects gas phase equilibria
- Distribution law accounts for competition inherently
Correct Answer: Competition changes phase composition and available space for solute solvation, altering apparent partitioning
Q37. Why might log P measured using octanol/water differ from in vivo lipid distribution?
- Octanol perfectly mimics all biological membranes
- Octanol/water system is a model; real membranes have proteins, different lipid composition and active transport mechanisms that change distribution
- In vivo lipids are identical to octanol chemically
- Because in vivo temperature is always lower than lab temperature
Correct Answer: Octanol/water system is a model; real membranes have proteins, different lipid composition and active transport mechanisms that change distribution
Q38. What is the impact of pH on distribution coefficient (D) for a weak base as pH increases above its pKa?
- D increases because more drug becomes ionized and partitions into organic phase
- D decreases because more drug becomes unionized and partitions more into organic phase
- D increases because more drug becomes unionized and partitions into organic phase
- D decreases because more drug becomes ionized and remains in aqueous phase
Correct Answer: D decreases because more drug becomes ionized and remains in aqueous phase
Q39. Which limitation explains why very concentrated solutions deviate from distribution law?
- At high concentration, interactions between solute molecules (association, nonideal activity coefficients) cause non-linear behavior and deviations
- High concentration always improves law applicability
- Distribution law assumes concentrated solutions only
- Concentration has no effect if solvents are immiscible
Correct Answer: At high concentration, interactions between solute molecules (association, nonideal activity coefficients) cause non-linear behavior and deviations
Q40. Which of the following is TRUE about log D vs log P?
- Log P accounts for ionization at given pH, log D does not
- Log D is pH-dependent and accounts for all species, while log P refers to the un-ionized form and is pH-independent
- Both are always identical
- Log P is used only for inorganic ions
Correct Answer: Log D is pH-dependent and accounts for all species, while log P refers to the un-ionized form and is pH-independent
Q41. How can one experimentally detect that association or complexation is causing distribution deviations?
- By measuring partition at multiple concentrations and observing concentration dependence of the ratio
- By assuming single concentration is sufficient
- By ignoring temperature effects
- By never changing phase composition
Correct Answer: By measuring partition at multiple concentrations and observing concentration dependence of the ratio
Q42. Why might a highly lipophilic drug show poor absorption despite high log P?
- Because extremely lipophilic drugs may be too strongly retained in membranes or insoluble in aqueous media, reducing effective absorption
- High log P always guarantees excellent absorption
- Because log P measures only ionized species
- Because lipophilicity prevents membrane contact
Correct Answer: Because extremely lipophilic drugs may be too strongly retained in membranes or insoluble in aqueous media, reducing effective absorption
Q43. In presence of metal ions that catalyze degradation in one phase, measured partition will be:
- Unchanged because degradation is irrelevant
- Altered because the parent compound concentration changes over time, invalidating equilibrium assumptions
- Always higher for degraded products
- Improved because degradation simplifies analysis
Correct Answer: Altered because the parent compound concentration changes over time, invalidating equilibrium assumptions
Q44. Which statement about activity coefficients and distribution law is correct?
- Distribution law uses activities; deviations occur when concentrations do not approximate activities due to non-ideal behavior
- Activity coefficients are irrelevant in distribution measurements
- Activities always equal concentrations in real systems
- Activity coefficients are constant across all solvents
Correct Answer: Distribution law uses activities; deviations occur when concentrations do not approximate activities due to non-ideal behavior
Q45. How does partitioning into bilayer membranes differ from octanol/water partitioning?
- Bilayers lack protein and are exactly like octanol
- Bilayers have organized lipid phases, headgroup interactions and embedded proteins making partitioning site-specific and sometimes energy-dependent
- Bilayer partitioning is always faster and identical numerically to octanol/water
- Octanol/water is a worse model because it forms micelles
Correct Answer: Bilayers have organized lipid phases, headgroup interactions and embedded proteins making partitioning site-specific and sometimes energy-dependent
Q46. Which corrective step is recommended when micellization is suspected in distribution experiments?
- Increase surfactant concentration further
- Work below CMC or remove surfactant/co-solute, or use models accounting for micellar solubilization
- Assume micelles do not affect results
- Use higher temperature to break micelles always
Correct Answer: Work below CMC or remove surfactant/co-solute, or use models accounting for micellar solubilization
Q47. Which limitation explains why enantiomers may show different tissue distribution though chemically similar?
- Enantiomers always distribute identically
- Chiral interactions with proteins, enzymes and membranes create stereoselective partitioning and binding
- Because enantiomers have different molecular weights
- Because one enantiomer is gaseous
Correct Answer: Chiral interactions with proteins, enzymes and membranes create stereoselective partitioning and binding
Q48. What is the role of activity vs concentration when interpreting deviations from distribution law?
- Concentration always equals activity in dilute solutions; deviations due to nonideal activity coefficients cause distribution ratio to vary with concentration
- Activity is irrelevant in thermodynamics
- Activity is only needed for gases
- Activities are automatically corrected during measurement
Correct Answer: Concentration always equals activity in dilute solutions; deviations due to nonideal activity coefficients cause distribution ratio to vary with concentration
Q49. For weak acids, which pH condition favors partition into organic solvent?
- pH well below pKa where acid is predominantly unionized
- pH well above pKa where acid is ionized
- Any pH has equal partition
- Only pH equal to 14 matters
Correct Answer: pH well below pKa where acid is predominantly unionized
Q50. Which summary statement best captures the practical limitation of applying distribution law to drug development?
- Distribution law is universally accurate and needs no adjustment in formulation or prediction
- Distribution law offers a useful theoretical basis, but real systems require consideration of ionization, complexation, binding, kinetics and experimental artifactual effects to make meaningful predictions for formulations and ADME
- Distribution law is irrelevant and should be ignored in all pharmaceutical contexts
- Distribution law predicts pharmacological potency directly
Correct Answer: Distribution law offers a useful theoretical basis, but real systems require consideration of ionization, complexation, binding, kinetics and experimental artifactual effects to make meaningful predictions for formulations and ADME
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.
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