Applications of distribution law MCQs With Answer is an essential review for B. Pharm students preparing for pharmacokinetics and pharmaceutical analysis. This introduction covers key concepts like Nernst distribution law, partition coefficient (P), distribution coefficient (D), pH-partition hypothesis, solvent selection, extraction techniques, and implications for drug absorption, tissue distribution, and bioavailability. These SEO-friendly MCQs with answers emphasize calculation, interpretation, and real-world applications—shake-flask method, chromatography correlation, ionization effects, protein binding influence, and formulation strategies. Mastering these topics will strengthen exam performance and practical lab skills in drug development. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What does the Nernst distribution law describe?
- The ratio of vapor pressures of a solute in two gases
- The equilibrium concentration ratio of an un-ionized solute between two immiscible solvents
- The rate of dissolution of a solute in a single solvent
- The ionic strength dependence of a solute’s solubility
Correct Answer: The equilibrium concentration ratio of an un-ionized solute between two immiscible solvents
Q2. The partition coefficient (P) is defined as:
- The ratio of total solute concentration in water to that in oil
- The ratio of solute concentration in organic phase to aqueous phase for the unionized form
- The ratio of ionized to unionized solute in one phase
- The solubility product of a drug in two solvents
Correct Answer: The ratio of solute concentration in organic phase to aqueous phase for the unionized form
Q3. Which experimental method is commonly used to measure partition coefficient?
- Gel electrophoresis
- Shake-flask method
- NMR spectroscopy only
- Thermogravimetric analysis
Correct Answer: Shake-flask method
Q4. For a weak acid, the fraction un-ionized at pH 3 given pKa 4 is best described by:
- Approximately 9:1 ionized to unionized
- Approximately 1:9 ionized to unionized
- About 50% unionized
- Completely ionized
Correct Answer: Approximately 9:1 ionized to unionized
Q5. The distribution coefficient (D) differs from partition coefficient (P) because D:
- Considers only the salt form of the drug
- Accounts for both ionized and unionized species at a given pH
- Is independent of pH
- Is always higher than P
Correct Answer: Accounts for both ionized and unionized species at a given pH
Q6. Which factor does NOT significantly affect distribution between two immiscible solvents?
- Temperature
- Ionic strength of aqueous phase
- pH (for ionizable drugs)
- Color of the solute
Correct Answer: Color of the solute
Q7. According to pH-partition hypothesis, a basic drug will be more absorbed in:
- Acidic environment where it exists mostly ionized
- Acidic environment where it exists mostly unionized
- Basic environment where it exists mostly ionized
- Basic environment where it exists mostly unionized
Correct Answer: Basic environment where it exists mostly unionized
Q8. Which expression gives the distribution ratio (D) for a monoprotic weak acid?
- D = P × (1 + 10^(pKa – pH))
- D = P / (1 + 10^(pH – pKa))
- D = P × (1 / (1 + 10^(pH – pKa)))
- D = P × (1 + 10^(pH – pKa))
Correct Answer: D = P / (1 + 10^(pH – pKa))
Q9. Which property is directly related to drug lipophilicity used in distribution studies?
- Melting point
- Partition coefficient (log P)
- Viscosity
- Optical rotation
Correct Answer: Partition coefficient (log P)
Q10. Salting out increases extraction into the organic phase by:
- Increasing aqueous solubility of the solute
- Decreasing aqueous solubility of the solute
- Changing the pKa of the solute
- Forming covalent bonds with the solute
Correct Answer: Decreasing aqueous solubility of the solute
Q11. In liquid-liquid extraction of a weak base, to extract it into aqueous phase you would:
- Adjust pH to make the base unionized
- Adjust pH to make the base ionized
- Add non-polar solvent to increase partitioning into organic
- Increase temperature only
Correct Answer: Adjust pH to make the base ionized
Q12. If a drug has log P = 4, what general property does it have?
- Highly hydrophilic
- Moderately lipophilic
- Highly lipophilic
- Extremely water soluble
Correct Answer: Highly lipophilic
Q13. Which statement about ionization and partitioning is correct?
- Ionized species preferentially partition into nonpolar solvents
- Unionized species preferentially partition into nonpolar solvents
- Ionization state has no effect on partitioning
- Only salts partition into nonpolar solvents
Correct Answer: Unionized species preferentially partition into nonpolar solvents
Q14. The Henderson-Hasselbalch equation is used in distribution studies to:
- Calculate the melting point of drug salts
- Estimate fraction ionized at a given pH
- Measure partition coefficient directly
- Determine stereochemistry of drug molecules
Correct Answer: Estimate fraction ionized at a given pH
Q15. Which application of distribution law is important in chromatography?
- Predicting elution order based on solvent partitioning
- Determining refractive index of mobile phase
- Calculating column pressure only
- Measuring particle size of the stationary phase
Correct Answer: Predicting elution order based on solvent partitioning
Q16. Which parameter would best predict a drug’s ability to cross biological membranes?
- Partition coefficient (log P)
- Boiling point
- Coefficient of thermal expansion
- Color index
Correct Answer: Partition coefficient (log P)
Q17. For a weak base with pKa 8, at pH 6 the majority of the drug exists as:
- Unionized base
- Ionized conjugate acid
- Undissociated acid
- Nonexistent
Correct Answer: Ionized conjugate acid
Q18. In a two-phase extraction, multiple extractions with smaller volumes of solvent are often preferred because:
- They reduce total solvent polarity
- They increase overall recovery of solute
- They change the pKa of the solute
- They prevent equilibrium from being reached
Correct Answer: They increase overall recovery of solute
Q19. Which phenomenon explains why adding electrolyte to aqueous phase changes distribution?
- Salting in only
- Salting out altering solubility
- Polarization of organic solvent
- Formation of emulsions only
Correct Answer: Salting out altering solubility
Q20. The partition coefficient is most reliably measured under conditions where:
- The solute is fully ionized
- The solute is fully unionized
- The solute is chemically reacting with solvent
- The solute concentration is above saturation in one phase
Correct Answer: The solute is fully unionized
Q21. A drug with very high distribution into tissues relative to plasma likely has:
- Low lipophilicity and low protein binding
- High lipophilicity and high tissue affinity
- High water solubility only
- Extremely low molecular weight causing exhalation
Correct Answer: High lipophilicity and high tissue affinity
Q22. Which is the correct reason protein binding affects distribution?
- Protein-bound drug can freely cross membranes
- Protein-bound drug is pharmacologically active and non-diffusible
- Only free drug can equilibrate between plasma and tissues
- Protein binding changes the drug’s chemical structure
Correct Answer: Only free drug can equilibrate between plasma and tissues
Q23. Which solvent property most strongly correlates with solute partitioning into that solvent?
- Color
- Polarity
- Electrical conductivity
- Viscosity at high shear
Correct Answer: Polarity
Q24. For a weak acid drug (pKa 5), which pH will favor extraction into organic solvent?
- pH 3
- pH 7
- pH 5
- pH 9
Correct Answer: pH 3
Q25. The log D value at a given pH is 2. What does this indicate?
- Distribution favors aqueous phase by 100-fold
- Distribution favors organic phase by 100-fold
- Drug is equally distributed between phases
- Drug is completely ionized
Correct Answer: Distribution favors organic phase by 100-fold
Q26. Which calculation must be performed to convert P into D for a monoprotic weak base?
- Multiply P by fraction ionized
- Divide P by (1 + 10^(pKa – pH))
- Multiply P by (1 + 10^(pKa – pH))
- Ignore pH and use P directly
Correct Answer: Multiply P by (1 + 10^(pKa – pH))
Q27. In biopharmaceutics, distribution law concepts help predict:
- Formulation color changes
- Drug absorption and tissue penetration
- Mechanical stability of tablets
- Tablet dissolution vessel size
Correct Answer: Drug absorption and tissue penetration
Q28. A drug shows higher partitioning into octanol than water. This suggests:
- Higher affinity for polar environments
- Greater lipophilicity and membrane permeability
- Lower potential for passive diffusion
- Complete ionization in biological fluids
Correct Answer: Greater lipophilicity and membrane permeability
Q29. The effect of temperature on distribution coefficient is typically:
- Negligible for all solutes
- Dependent on enthalpy change of transfer; may increase or decrease
- Always increases D with rising temperature
- Always decreases D with rising temperature
Correct Answer: Dependent on enthalpy change of transfer; may increase or decrease
Q30. Which is a limitation when using shake-flask method for partition coefficient?
- Inability to separate phases
- Emulsion formation and slow equilibration for some compounds
- It gives pKa values directly
- Requires radioactive labeling always
Correct Answer: Emulsion formation and slow equilibration for some compounds
Q31. Which term describes the effect where a drug distributes between plasma and red blood cells?
- Volume of absorption
- Partitioning into blood components
- Elimination constant
- Metabolic clearance
Correct Answer: Partitioning into blood components
Q32. Which tool often correlates log P with membrane permeability in early drug discovery?
- Thermogravimetry
- Lipinski’s rule of five and log P estimations
- Mass spectrometry for impurities
- Atomic absorption spectroscopy
Correct Answer: Lipinski’s rule of five and log P estimations
Q33. What happens to the distribution of a weak acid when pH >> pKa?
- Mostly unionized and partitions into organic phase
- Mostly ionized and remains in aqueous phase
- Precipitates out
- Becomes covalently bonded to solvent
Correct Answer: Mostly ionized and remains in aqueous phase
Q34. Which of the following best describes distribution ratio (D) experimentally?
- Concentration in organic phase divided by concentration of unionized species in aqueous phase only
- Total concentration in organic phase divided by total concentration in aqueous phase at equilibrium
- Molecular weight times partition coefficient
- Square of partition coefficient
Correct Answer: Total concentration in organic phase divided by total concentration in aqueous phase at equilibrium
Q35. For a diprotic acid, distribution behavior compared to monoprotic acid is:
- Independent of pH
- Dependent on two pKa values and more complex pH-dependence
- Always more lipophilic
- Always fully ionized at physiological pH
Correct Answer: Dependent on two pKa values and more complex pH-dependence
Q36. Which laboratory consideration improves accuracy of partition coefficient measurement?
- Using volumes that cause saturation only in organic phase
- Ensuring equilibrium by sufficient mixing and time
- Measuring immediately without phase separation
- Using colored solvents to track partitioning
Correct Answer: Ensuring equilibrium by sufficient mixing and time
Q37. Which application uses distribution law in formulation of topical drugs?
- Predicting drug partitioning into skin lipids vs. aqueous layers
- Calculating tablet hardness
- Designing capsule size
- Measuring pH of bulk solvent only
Correct Answer: Predicting drug partitioning into skin lipids vs. aqueous layers
Q38. When performing solvent extraction, which organic solvent property is most desirable for better extraction of nonpolar drug?
- High dielectric constant
- High polarity
- Low polarity and miscibility with aqueous phase
- Ability to form hydrogen bonds with water
Correct Answer: Low polarity and miscibility with aqueous phase
Q39. Which of these is a practical use of partition coefficient in drug development?
- Selecting colorants for dosage forms
- Estimating oral bioavailability and permeability
- Measuring tablet friability
- Choosing packaging materials only
Correct Answer: Estimating oral bioavailability and permeability
Q40. If log P decreases when ionization is considered at physiological pH, this means:
- Drug becomes more lipophilic at physiological pH
- Drug becomes less lipophilic (more hydrophilic) at physiological pH
- pH has no effect on lipophilicity
- Log P is unrelated to pH
Correct Answer: Drug becomes less lipophilic (more hydrophilic) at physiological pH
Q41. Which is true about distribution of stereoisomers in two-phase systems?
- Stereoisomers always have identical partitioning
- Stereoisomers can have different partition coefficients due to stereospecific interactions
- Stereoisomers only differ in color, not partitioning
- Stereoisomers cannot be separated by partitioning methods
Correct Answer: Stereoisomers can have different partition coefficients due to stereospecific interactions
Q42. Which parameter helps estimate drug accumulation in fatty tissues?
- Log P and lipophilicity
- Water activity only
- Salt index
- Refractive index
Correct Answer: Log P and lipophilicity
Q43. A drug with log P ~ 0 suggests:
- Equal affinity for octanol and water
- Strongly lipophilic
- Strongly hydrophobic
- Inability to be absorbed orally
Correct Answer: Equal affinity for octanol and water
Q44. Which condition would favor extraction of a weak base into organic solvent?
- High aqueous pH to keep base unionized
- Low aqueous pH to ionize the base
- Adding strong oxidizer
- Reducing ionic strength drastically
Correct Answer: High aqueous pH to keep base unionized
Q45. Why is log D more practical than log P for biological predictions?
- Log D accounts for ionization at physiological pH
- Log D ignores pH effects entirely
- Log D only applies to non-ionizable drugs
- Log D is always equal to log P
Correct Answer: Log D accounts for ionization at physiological pH
Q46. In distributing a drug between blood and tissue, which is a major driving factor?
- Drug’s magnetic susceptibility
- Lipophilicity and tissue affinity
- Tablet excipient composition
- Light exposure only
Correct Answer: Lipophilicity and tissue affinity
Q47. Which analytical method may determine partitioning alongside concentration measurement?
- HPLC of separated phases
- Thermal conductivity detector only
- Optical microscopy
- Gravimetric analysis of organic solvent
Correct Answer: HPLC of separated phases
Q48. A drug with high plasma protein binding will have:
- Greater fraction of free drug available for distribution
- Smaller free fraction available to distribute into tissues
- Faster passive diffusion globally
- No impact on distribution
Correct Answer: Smaller free fraction available to distribute into tissues
Q49. How does micellar solubilization affect apparent distribution of a drug?
- It can increase apparent aqueous solubility, reducing partitioning into organic phase
- It always decreases aqueous solubility
- It converts drug to a volatile form
- It eliminates ionization effects
Correct Answer: It can increase apparent aqueous solubility, reducing partitioning into organic phase
Q50. Which strategy can be used to enhance extraction efficiency of a weak acid into organic solvent?
- Adjust pH above its pKa
- Adjust pH below its pKa to favor unionized form
- Add strong base to form salts
- Increase ionic strength to form complexes with water
Correct Answer: Adjust pH below its pKa to favor unionized form

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