Physicochemical properties and drug activity explores how molecular characteristics such as solubility, lipophilicity (log P/log D), pKa, permeability, crystal form, and stability influence drug absorption, distribution, metabolism, excretion, and pharmacodynamics. For B.Pharm students, mastering these concepts links chemistry to therapeutic effect—predicting bioavailability, optimizing salt forms, designing prodrugs, and selecting assays (e.g., Caco-2, PAMPA, shake-flask). Key topics include Henderson-Hasselbalch relationships, partitioning across membranes, particle size and dissolution (Noyes‑Whitney), polymorphism, and formulation strategies to enhance stability and activity. Understanding these properties is essential for rational drug development and quality control. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What does the partition coefficient (log P) primarily measure?
- The ratio of ionized drug in water to octanol
- The ratio of unionized drug concentration in octanol to water
- The rate of drug dissolution in aqueous media
- The drug’s ability to bind plasma proteins
Correct Answer: The ratio of unionized drug concentration in octanol to water
Q2. Which equation relates pH, pKa, and the ratio of ionized to unionized species?
- Noyes‑Whitney equation
- Henderson‑Hasselbalch equation
- Arrhenius equation
- Michaelis‑Menten equation
Correct Answer: Henderson‑Hasselbalch equation
Q3. Which property most strongly influences passive diffusion across lipid membranes?
- Hydrogen bond donor count
- Polar surface area
- Lipophilicity (log P/log D)
- Melting point
Correct Answer: Lipophilicity (log P/log D)
Q4. What is log D different from log P?
- Log D measures only unionized drug; log P measures total drug
- Log D is pH-dependent partitioning of all species; log P is partitioning of the neutral form
- Log D is measured in octanol/hexane; log P is measured in octanol/water
- Log D measures dissolution rate; log P measures permeability
Correct Answer: Log D is pH-dependent partitioning of all species; log P is partitioning of the neutral form
Q5. Which factor reduces aqueous solubility of a drug?
- Presence of polar functional groups
- Low crystal lattice energy
- High lipophilicity
- Small particle size
Correct Answer: High lipophilicity
Q6. Higuchi and Noyes‑Whitney equations describe which process?
- Drug absorption into tissues
- Dissolution and release rate from solids
- Membrane permeability kinetics
- Enzymatic drug metabolism
Correct Answer: Dissolution and release rate from solids
Q7. Which solid-state property can alter dissolution and bioavailability?
- Polymorphism
- Optical rotation
- Atomic weight
- Vapor pressure
Correct Answer: Polymorphism
Q8. Ionization of a weak acid drug (pKa 4.5) in stomach pH 1.5 will be mostly:
- Ionized and highly soluble
- Unionized and more membrane permeable
- Completely degraded
- Protein bound
Correct Answer: Unionized and more membrane permeable
Q9. Which assay is commonly used to estimate intestinal permeability in vitro?
- Shake‑flask solubility
- Caco‑2 cell monolayer
- DSC (Differential Scanning Calorimetry)
- Mass spectrometry
Correct Answer: Caco‑2 cell monolayer
Q10. Salt formation is primarily used to:
- Increase molecular weight
- Modify melting point only
- Enhance solubility and dissolution rate
- Change pharmacological target
Correct Answer: Enhance solubility and dissolution rate
Q11. Which characteristic is part of Lipinski’s Rule of Five?
- Molecular weight less than 500 Da
- More than 10 hydrogen bond donors
- Log P greater than 6
- PSA greater than 200 Ų
Correct Answer: Molecular weight less than 500 Da
Q12. What effect does increasing pH have on the solubility of a weak base?
- Decreases solubility
- Increases solubility
- No effect
- Catalyzes degradation
Correct Answer: Decreases solubility
Q13. Which property is directly increased by reducing particle size?
- Partition coefficient
- Dissolution rate
- pKa
- Caco‑2 permeability
Correct Answer: Dissolution rate
Q14. Protonation state affects permeability because:
- Ionized species cross lipid membranes more readily
- Unionized species are more lipophilic and cross membranes easier
- Protein binding is independent of ionization
- pKa changes with membrane composition
Correct Answer: Unionized species are more lipophilic and cross membranes easier
Q15. Which method measures partition coefficient experimentally?
- Shake‑flask (octanol/water)
- IR spectroscopy
- Chromatographic melting analysis
- Dynamic light scattering
Correct Answer: Shake‑flask (octanol/water)
Q16. A high polar surface area (PSA) generally correlates with:
- Increased membrane permeability
- Decreased oral absorption
- Higher lipophilicity
- Lower aqueous solubility
Correct Answer: Decreased oral absorption
Q17. Ion trapping across membranes occurs when:
- A drug is neutral on both sides of a membrane
- pH difference causes accumulation of ionized form in one compartment
- Protein binding prevents membrane crossing
- Drug degrades before permeation
Correct Answer: pH difference causes accumulation of ionized form in one compartment
Q18. Which degradation pathway is most influenced by aqueous pH?
- Photolysis
- Hydrolysis
- Oxidation by air
- Polymorphic conversion
Correct Answer: Hydrolysis
Q19. Which formulation approach can improve permeability of a poorly permeable drug?
- Convert to a less lipophilic salt
- Use prodrug strategy to increase lipophilicity
- Increase crystalline order
- Add water‑soluble fillers only
Correct Answer: Use prodrug strategy to increase lipophilicity
Q20. Protein binding primarily affects which pharmacokinetic parameter?
- Intrinsic chemical stability
- Volume of distribution and free fraction
- Crystal form of the drug
- pKa of the drug
Correct Answer: Volume of distribution and free fraction
Q21. Which molecular feature tends to decrease metabolic stability?
- Bulky steric hindrance near metabolic sites
- Highly polar, flexible regions accessible to enzymes
- Fluorination at metabolically labile positions
- Conjugation to make rigid scaffold
Correct Answer: Highly polar, flexible regions accessible to enzymes
Q22. Which analytical technique assesses solid-state transitions and polymorphs?
- Caco‑2 permeability assay
- Differential Scanning Calorimetry (DSC)
- Shake‑flask partitioning
- PAMPA assay
Correct Answer: Differential Scanning Calorimetry (DSC)
Q23. A drug with log P = 5 is likely to have which issue?
- Excessive aqueous solubility
- Poor membrane permeability
- Low oral bioavailability due to poor solubility
- High PSA
Correct Answer: Low oral bioavailability due to poor solubility
Q24. Which descriptor estimates the total number of hydrogen bond donors and acceptors affecting permeability?
- Partition coefficient
- Topological polar surface area (TPSA)
- Melting point
- pKa
Correct Answer: Topological polar surface area (TPSA)
Q25. In Henderson‑Hasselbalch, for a weak acid, when pH = pKa, the ratio of ionized to unionized species is:
- 10:1
- 1:10
- 1:1
- 0:1
Correct Answer: 1:1
Q26. PAMPA is primarily used to study:
- Solid state polymorphism
- Artificial membrane passive permeability
- Enzyme kinetics
- Protein binding
Correct Answer: Artificial membrane passive permeability
Q27. Which excipient property can negatively affect drug chemical stability?
- Low hygroscopicity
- Presence of catalytic impurities or moisture
- Neutral, inert filler
- Hydrophobic coating
Correct Answer: Presence of catalytic impurities or moisture
Q28. Which strategy reduces first‑pass hepatic metabolism to improve bioavailability?
- Increase drug polarity
- Design a prodrug activated after absorption
- Choose a highly crystalline form
- Increase tablet hardness
Correct Answer: Design a prodrug activated after absorption
Q29. Which is true about amorphous vs crystalline drug forms?
- Amorphous forms are thermodynamically more stable
- Crystalline forms usually have higher solubility
- Amorphous forms often show higher apparent solubility and faster dissolution
- Crystalline forms always dissolve faster
Correct Answer: Amorphous forms often show higher apparent solubility and faster dissolution
Q30. Protein‑ligand interactions affecting activity are most directly influenced by which physicochemical property?
- Melting point
- Electronic distribution and molecular shape (complementarity)
- Bulk powder density
- Salt index
Correct Answer: Electronic distribution and molecular shape (complementarity)
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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