Introduction: Understanding the partition coefficient and its influence on biological action is essential for B.Pharm students involved in drug design, pharmacokinetics, and formulation. The partition coefficient (P) or log P measures a drug’s lipophilicity between octanol and water and predicts membrane permeability, absorption, distribution, blood–brain barrier penetration, and metabolic stability. Mastery of log P, log D (pH-dependent distribution), ionization, and experimental methods (shake‑flask, chromatographic) helps optimize lead compounds for efficacy and safety. This primer emphasizes practical implications for ADME, protein binding, and formulation strategies in drug development. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What does the partition coefficient (P) measure in drug molecules?
- Distribution between lipid bilayers and proteins
- Ratio of drug concentration in octanol to water at equilibrium
- Rate of drug metabolism in the liver
- Extent of renal clearance
Correct Answer: Ratio of drug concentration in octanol to water at equilibrium
Q2. How is log P defined?
- The negative logarithm of the partition coefficient
- The base-10 logarithm of the partition coefficient
- The natural logarithm of the distribution coefficient
- The difference between log D and pKa
Correct Answer: The base-10 logarithm of the partition coefficient
Q3. Which statement best distinguishes log P and log D?
- Log P accounts for ionization at given pH, log D does not
- Log D is measured only in octanol, log P only in water
- Log P is for non-ionized species; log D is the pH-dependent distribution of all species
- Log P and log D are identical for weak acids at any pH
Correct Answer: Log P is for non-ionized species; log D is the pH-dependent distribution of all species
Q4. Which experimental method is considered the gold standard for measuring partition coefficients?
- SHIME assay
- Shake‑flask method
- Caco‑2 permeability assay
- Plasma protein binding assay
Correct Answer: Shake‑flask method
Q5. A drug with log P = 4 is likely to have which characteristic?
- Very high aqueous solubility and poor membrane permeation
- High lipophilicity, increased membrane permeation, but poor aqueous solubility
- High polarity and inability to cross cell membranes
- Ideal hydrophilicity for renal excretion
Correct Answer: High lipophilicity, increased membrane permeation, but poor aqueous solubility
Q6. Why is lipophilicity important for blood–brain barrier (BBB) penetration?
- Highly hydrophilic drugs preferentially cross the BBB
- Moderate lipophilicity favors passive diffusion across the BBB
- Only charged molecules can cross the BBB efficiently
- Lipophilicity does not affect BBB penetration
Correct Answer: Moderate lipophilicity favors passive diffusion across the BBB
Q7. How does ionization affect the measured partitioning of a weak acid at acidic pH?
- Ionized form increases partitioning into octanol
- Non-ionized form predominates and increases partitioning into octanol
- Ionization has no effect on partitioning
- Ionized form always partitions into octanol more than water
Correct Answer: Non-ionized form predominates and increases partitioning into octanol
Q8. Which parameter is most useful to predict oral absorption in early drug discovery?
- Partition coefficient (log P) combined with molecular size and hydrogen bonding capacity
- Only plasma protein binding percentage
- Only volume of distribution
- Only metabolic half‑life
Correct Answer: Partition coefficient (log P) combined with molecular size and hydrogen bonding capacity
Q9. A drug with log P ≈ 0 is expected to be:
- Extremely lipophilic and sequestered in tissues
- Highly hydrophilic and likely to have low membrane permeability
- Balanced between aqueous and lipid phases, favoring some permeability and solubility
- Completely insoluble in water
Correct Answer: Balanced between aqueous and lipid phases, favoring some permeability and solubility
Q10. How does high lipophilicity generally affect metabolic stability?
- Increases clearance due to enhanced renal elimination
- Often increases metabolic clearance due to greater affinity for metabolic enzymes
- Has no effect on metabolism
- Always prevents metabolism by P450 enzymes
Correct Answer: Often increases metabolic clearance due to greater affinity for metabolic enzymes
Q11. Which in silico descriptor is directly derived from partition coefficient?
- pKa
- Log P (calculated) or clog P
- Intrinsic clearance
- Percentage bioavailability
Correct Answer: Log P (calculated) or clog P
Q12. Which log P range is commonly considered optimal for oral drugs (Lipinski’s rule of five guidance)?
- Log P greater than 5
- Log P less than or equal to 5
- Log P exactly 0
- Log P less than −2
Correct Answer: Log P less than or equal to 5
Q13. What is the primary reason extremely high log P compounds show low oral bioavailability?
- Excessive water solubility
- Poor aqueous solubility leading to dissolution-limited absorption
- Enhanced transporter-mediated uptake
- Inability to bind to plasma proteins
Correct Answer: Poor aqueous solubility leading to dissolution-limited absorption
Q14. Which chromatographic technique can be used to estimate lipophilicity as an alternative to shake‑flask?
- Size‑exclusion chromatography
- Reverse-phase HPLC retention time correlation
- Ion-exchange chromatography
- Gel electrophoresis
Correct Answer: Reverse-phase HPLC retention time correlation
Q15. How does plasma protein binding relate to lipophilicity?
- More lipophilic drugs generally show higher plasma protein binding
- More lipophilic drugs always have zero plasma protein binding
- Less lipophilic drugs always bind more to plasma proteins
- Lipophilicity and protein binding are unrelated
Correct Answer: More lipophilic drugs generally show higher plasma protein binding
Q16. Which effect does increasing hydrogen-bond donors and acceptors generally have on log P?
- Increase log P by enhancing lipophilicity
- Decrease log P by increasing polarity and water affinity
- No change in log P
- Convert log P to log D
Correct Answer: Decrease log P by increasing polarity and water affinity
Q17. Why is log D measured at physiological pH important for predicting in vivo behavior?
- Because it ignores ionized drug species
- Because it reflects distribution of all species (ionized + unionized) at that pH
- Because it equals log P at all pH values
- Because it measures only protein-bound drug
Correct Answer: Because it reflects distribution of all species (ionized + unionized) at that pH
Q18. A basic drug with pKa 9 will be mostly ionized in which environment?
- pH 2
- pH 10
- pH 9
- pH 14
Correct Answer: pH 2
Q19. What is the impact of ionization on membrane permeability?
- Ionized species generally cross lipid membranes more readily than unionized species
- Ionization has no effect on permeability
- Unionized species generally cross lipid membranes more readily than ionized species
- Only charged species can use passive diffusion
Correct Answer: Unionized species generally cross lipid membranes more readily than ionized species
Q20. Which of the following changes would likely increase a drug’s log P?
- Addition of polar hydroxyl groups
- Methylation of a polar amine to a tertiary amine (reducing polarity)
- Conversion of an aromatic ring to a carboxylic acid
- Introduction of multiple charged groups
Correct Answer: Methylation of a polar amine to a tertiary amine (reducing polarity)
Q21. In QSAR modeling, why is log P often included as a descriptor?
- Because it predicts crystal structure
- Because lipophilicity influences potency, permeability, and ADME properties
- Because it directly measures receptor binding kinetics
- Because it indicates the drug’s manufacturing cost
Correct Answer: Because lipophilicity influences potency, permeability, and ADME properties
Q22. Which biological action is most directly influenced by a drug’s partition coefficient?
- Electrolyte balance
- Membrane permeability and tissue distribution
- Enzymatic catalytic mechanism
- DNA replication fidelity
Correct Answer: Membrane permeability and tissue distribution
Q23. How does increased lipophilicity affect volume of distribution (Vd)?
- Often leads to decreased Vd due to retention in plasma
- Often leads to increased Vd due to tissue partitioning
- Has no predictable effect on Vd
- Always reduces Vd to zero
Correct Answer: Often leads to increased Vd due to tissue partitioning
Q24. Which of the following is true for a zwitterionic drug regarding partitioning?
- It always has very high log P
- Net neutrality at certain pH can increase lipophilicity and partitioning
- Zwitterions cannot partition into octanol
- They are always trapped in the aqueous phase
Correct Answer: Net neutrality at certain pH can increase lipophilicity and partitioning
Q25. Which factor does NOT directly affect measured log P in shake‑flask experiments?
- Choice of octanol grade and water purity
- Temperature during equilibration
- pH of the aqueous phase when measuring non-ionizable compounds
- Duration allowed for equilibration
Correct Answer: pH of the aqueous phase when measuring non-ionizable compounds
Q26. A drug with log D (pH 7.4) << log P indicates:
- Significant ionization at pH 7.4 reducing apparent lipophilicity
- Enhanced lipophilicity at physiological pH
- That log P was measured incorrectly
- No ionization occurs at pH 7.4
Correct Answer: Significant ionization at pH 7.4 reducing apparent lipophilicity
Q27. Which cellular assay correlates with passive permeability and is influenced by lipophilicity?
- MTT cytotoxicity assay
- Caco‑2 monolayer permeability assay
- Western blot for P‑glycoprotein
- ELISA for cytokines
Correct Answer: Caco‑2 monolayer permeability assay
Q28. In formulation, how can high lipophilicity-related poor solubility be addressed?
- Formulation as prodrug, lipid-based formulation, or solid dispersion to enhance solubility
- Always increase particle size
- Avoid any excipients and use pure drug powder orally
- Reduce temperature of storage to −80°C
Correct Answer: Formulation as prodrug, lipid-based formulation, or solid dispersion to enhance solubility
Q29. Which statement about amphipathic drugs is correct?
- They have both hydrophilic and lipophilic regions, influencing membrane interactions and distribution
- They are entirely hydrophobic and insoluble in water
- They cannot cross membranes under any conditions
- Their partition coefficient is always negative
Correct Answer: They have both hydrophilic and lipophilic regions, influencing membrane interactions and distribution
Q30. Why is log P important in predicting topical drug absorption?
- Highly hydrophilic molecules always permeate skin easily
- Moderate lipophilicity favors partitioning into stratum corneum lipids and improves topical absorption
- Only molecule size matters for topical absorption
- Topical absorption is independent of lipophilicity
Correct Answer: Moderate lipophilicity favors partitioning into stratum corneum lipids and improves topical absorption
Q31. Which of the following best explains the relationship between log P and oral first‑pass metabolism?
- Higher log P always eliminates first‑pass metabolism
- High lipophilicity may increase hepatic uptake and first‑pass metabolism
- Log P does not influence hepatic clearance
- Low log P ensures extensive first‑pass metabolism
Correct Answer: High lipophilicity may increase hepatic uptake and first‑pass metabolism
Q32. What is the effect of acylation (adding an acyl group) on a drug’s lipophilicity?
- Typically increases lipophilicity and log P
- Always makes the drug hydrophilic
- Has no effect on polarity
- Always causes ionization at physiological pH
Correct Answer: Typically increases lipophilicity and log P
Q33. Which property is a consequence of a drug having very low log P (high hydrophilicity)?
- Enhanced passive membrane permeation
- Predominant renal excretion and limited tissue distribution
- High tendency for tissue accumulation in fat
- Strong plasma protein binding
Correct Answer: Predominant renal excretion and limited tissue distribution
Q34. In drug discovery, why might a medicinal chemist seek to reduce log P of a lead compound?
- To decrease aqueous solubility
- To reduce off‑target toxicity, improve solubility, and optimize ADME profile
- To ensure the compound becomes permanently protein bound
- To guarantee BBB penetration
Correct Answer: To reduce off‑target toxicity, improve solubility, and optimize ADME profile
Q35. Which is TRUE about octanol as the organic phase in partition experiments?
- Octanol perfectly mimics biological membranes but is hydrophilic
- Octanol is a compromise solvent representing lipid-like environment though not identical to bilayers
- Octanol is completely non-polar and does not interact with solutes
- Octanol cannot solubilize lipophilic drugs
Correct Answer: Octanol is a compromise solvent representing lipid-like environment though not identical to bilayers
Q36. How does temperature influence partition coefficient measurements?
- Temperature has no effect
- Increasing temperature typically alters solubility and can change measured partitioning
- Only pressure affects partition coefficient
- Partition coefficient is defined only at 0°C
Correct Answer: Increasing temperature typically alters solubility and can change measured partitioning
Q37. For a weak acid with pKa 4.5, at pH 7.4 the predominant form is:
- Unionized
- Ionized (deprotonated)
- Zwitterionic
- Undetermined without log P
Correct Answer: Ionized (deprotonated)
Q38. What role does lipophilicity play in drug–receptor binding?
- No role; only ionic interactions matter
- Hydrophobic interactions often contribute to binding affinity and selectivity
- Lipophilicity always reduces binding affinity
- Lipophilicity only affects covalent bonding
Correct Answer: Hydrophobic interactions often contribute to binding affinity and selectivity
Q39. In preformulation, why measure log D at different pH values?
- To assess pH-dependent solubility, absorption, and distribution for various physiological environments
- To remove need for permeability studies
- Because log D is constant across pH
- Only to determine taste of the drug
Correct Answer: To assess pH-dependent solubility, absorption, and distribution for various physiological environments
Q40. Which molecular change would decrease passive intestinal permeability?
- Reducing molecular size and log P
- Increasing polarity and number of ionizable groups at intestinal pH
- Methylating polar groups to increase lipophilicity
- Prodrug formation to transiently increase lipophilicity
Correct Answer: Increasing polarity and number of ionizable groups at intestinal pH
Q41. Which statement about lipophilicity and toxicity is most accurate?
- Higher lipophilicity always ensures lower toxicity
- Higher lipophilicity can increase risk of off‑target interactions and toxicity
- Lipophilicity has no relationship to toxicity
- Only hydrophilic drugs are toxic
Correct Answer: Higher lipophilicity can increase risk of off‑target interactions and toxicity
Q42. Which analytical consideration is important when correlating HPLC retention times to log P?
- Column type, mobile phase composition and pH critically influence retention and must be standardized
- Retention time is independent of mobile phase
- Only detector wavelength matters for lipophilicity estimation
- Flow rate has no impact on retention behavior
Correct Answer: Column type, mobile phase composition and pH critically influence retention and must be standardized
Q43. How can prodrug strategies modify partitioning behavior?
- Prodrugs always reduce lipophilicity permanently
- Prodrugs can transiently increase lipophilicity to enhance absorption and be metabolized to active drug
- Prodrugs only affect color, not partitioning
- Prodrugs prevent blood–brain barrier crossing
Correct Answer: Prodrugs can transiently increase lipophilicity to enhance absorption and be metabolized to active drug
Q44. Which of the following best describes log P values for highly polar ionic drugs?
- Large positive log P values (e.g., >5)
- Negative or very low log P values indicating hydrophilicity
- Log P is always 1 for ionic drugs
- Log P equals molecular weight for ionic compounds
Correct Answer: Negative or very low log P values indicating hydrophilicity
Q45. Which ADME parameter is least directly related to partition coefficient?
- Plasma protein binding
- Renal clearance by glomerular filtration
- Tissue distribution
- Passive membrane permeability
Correct Answer: Renal clearance by glomerular filtration
Q46. When designing CNS drugs, which log P/log D characteristic is typically targeted?
- Extremely low log P to avoid BBB
- Moderate lipophilicity and low efflux liability to enable BBB penetration
- Very high log P with high efflux substrate potential
- Log D values are not considered for CNS drugs
Correct Answer: Moderate lipophilicity and low efflux liability to enable BBB penetration
Q47. How do efflux transporters like P‑glycoprotein interact with lipophilicity?
- P‑glycoprotein substrate recognition is unrelated to lipophilicity
- Many lipophilic compounds are P‑gp substrates and may be pumped out, reducing brain or cellular exposure
- P‑gp only transports hydrophilic molecules
- P‑gp permanently increases intracellular lipophilicity
Correct Answer: Many lipophilic compounds are P‑gp substrates and may be pumped out, reducing brain or cellular exposure
Q48. Which approach helps estimate log P for ionizable compounds more realistically?
- Ignoring ionization and using log P only
- Calculating log D at relevant physiological pH values
- Measuring partition in pure hexane instead of octanol
- Using molecular weight as a surrogate
Correct Answer: Calculating log D at relevant physiological pH values
Q49. Which statement about the relationship between solubility and log P is correct?
- Higher log P necessarily means higher aqueous solubility
- Higher log P often correlates with lower aqueous solubility
- Solubility and log P are identical properties
- Log P predicts solubility in all solvents accurately
Correct Answer: Higher log P often correlates with lower aqueous solubility
Q50. For a drug discovery candidate with borderline permeability and high plasma protein binding, which modification might improve free drug concentration?
- Increase lipophilicity further to enhance protein binding
- Introduce polar groups to reduce plasma protein binding and improve free fraction while balancing permeability
- Ignore ADME concerns and proceed to clinical trials
- Maximize molecular weight without changing polarity
Correct Answer: Introduce polar groups to reduce plasma protein binding and improve free fraction while balancing permeability
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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