Permeability method MCQs With Answer

Permeability method MCQs With Answer

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Permeability method MCQs With Answer

Understanding drug permeability is essential for B. Pharm students preparing for formulation and biopharmaceutics. This introduction covers key concepts such as permeability coefficient (Papp), flux, in vitro models (Caco-2, PAMPA), sink conditions, passive diffusion, paracellular vs transcellular routes, P-glycoprotein efflux, and the influence of pH, ionization and lipophilicity (log P) on absorption. Familiarity with experimental calculation, units (cm/s), and regulatory frameworks like BCS helps predict oral drug absorption and guide formulation strategies. Clear comprehension of these permeability concepts supports rational drug design and bioavailability optimization. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the apparent permeability coefficient (Papp) commonly used to describe?

  • The rate of chemical degradation of a drug in solution
  • The permeability of a compound across a biological membrane under specific experimental conditions
  • The maximum solubility of a drug in water
  • The partition coefficient between octanol and water

Correct Answer: The permeability of a compound across a biological membrane under specific experimental conditions

Q2. Which unit is typically used for expressing permeability coefficient (Papp)?

  • mol/L
  • cm/s
  • mg/mL
  • mM

Correct Answer: cm/s

Q3. In the equation J = P · C, what does J represent?

  • Partition coefficient
  • Flux (amount crossing per unit area per unit time)
  • Permeability of the membrane
  • Concentration gradient at equilibrium

Correct Answer: Flux (amount crossing per unit area per unit time)

Q4. Which in vitro model is best known for mimicking human intestinal epithelial permeability including active transporters?

  • PAMPA
  • Caco-2 cell monolayer
  • Shake-flask partitioning
  • HeLa cell culture

Correct Answer: Caco-2 cell monolayer

Q5. PAMPA primarily measures which type of permeability?

  • Transporter-mediated active uptake
  • Passive transcellular permeability through lipid membranes
  • Paracellular ionic flux via tight junctions
  • Enzymatic metabolism during absorption

Correct Answer: Passive transcellular permeability through lipid membranes

Q6. What does a high Papp value usually indicate about an oral drug candidate?

  • Low membrane permeability and poor absorption
  • High permeability and likely good intestinal absorption
  • High clearance by hepatic metabolism
  • Extensive plasma protein binding

Correct Answer: High permeability and likely good intestinal absorption

Q7. Which factor most directly increases paracellular permeability?

  • Increased lipophilicity (high log P)
  • Looser tight junctions between epithelial cells
  • Presence of P-glycoprotein efflux
  • Higher molecular rigidity

Correct Answer: Looser tight junctions between epithelial cells

Q8. How does ionization (pKa vs pH) influence permeability?

  • Only ionized forms permeate lipid membranes faster
  • Unionized forms generally penetrate lipid membranes more readily
  • Ionization has no effect on passive permeability
  • Ionized molecules always use transcellular routes

Correct Answer: Unionized forms generally penetrate lipid membranes more readily

Q9. Which property correlates most strongly with passive transcellular permeability?

  • Polar surface area (PSA)
  • Log P (lipophilicity)
  • Solubility in water
  • Melting point

Correct Answer: Log P (lipophilicity)

Q10. In a Caco-2 permeability assay, a high basolateral-to-apical apparent permeability compared to apical-to-basolateral suggests what?

  • Passive diffusion dominance
  • Active efflux transport (e.g., P-gp mediated)
  • Paracellular transport predominance
  • Assay contamination

Correct Answer: Active efflux transport (e.g., P-gp mediated)

Q11. What is the main limitation of PAMPA compared to Caco-2 assays?

  • Cannot measure passive permeability
  • Does not include transporter or metabolic activity
  • Too expensive for routine use
  • Requires living cells

Correct Answer: Does not include transporter or metabolic activity

Q12. Which mathematical expression defines apparent permeability (Papp) in a typical donor-acceptor assay?

  • Papp = (dQ/dt) / (A · C0)
  • Papp = C0 / (dQ/dt · A)
  • Papp = A · C0 / dQ/dt
  • Papp = log P · C0

Correct Answer: Papp = (dQ/dt) / (A · C0)

Q13. Sink conditions in permeability experiments mean:

  • The donor concentration is kept negligibly low
  • The acceptor concentration remains much lower than donor to maintain constant driving force
  • The membrane is saturated with drug
  • Permeability is measured after equilibrium is reached

Correct Answer: The acceptor concentration remains much lower than donor to maintain constant driving force

Q14. Which transport mechanism is energy-dependent and can limit oral absorption of substrates?

  • Passive diffusion
  • Facilitated diffusion
  • Active transporter efflux (e.g., P-gp)
  • Paracellular diffusion

Correct Answer: Active transporter efflux (e.g., P-gp)

Q15. A drug with high solubility but low permeability falls into which BCS class?

  • Class I
  • Class II
  • Class III
  • Class IV

Correct Answer: Class III

Q16. Which experimental observation indicates transcellular permeation rather than paracellular?

  • Permeability strongly correlates with lipophilicity (log P)
  • Permeability increases with molecular size
  • Permeability independent of pH
  • Permeability is higher for charged molecules

Correct Answer: Permeability strongly correlates with lipophilicity (log P)

Q17. Which descriptor often reduces passive permeability when high?

  • Low molecular weight
  • High polar surface area (>140 Ų)
  • Moderate lipophilicity (log P 1–3)
  • Low hydrogen bond donors

Correct Answer: High polar surface area (>140 Ų)

Q18. How does increasing temperature typically affect passive permeability in vitro?

  • Permeability decreases due to gelation
  • Permeability increases by accelerating diffusion
  • No change because permeability is temperature-independent
  • Permeability becomes negative

Correct Answer: Permeability increases by accelerating diffusion

Q19. What role does unstirred water layer (UWL) play in permeability measurements?

  • No role; it is always negligible
  • It can add resistance, lowering apparent permeability especially for very lipophilic drugs
  • It increases permeability by enhancing mixing
  • It converts active transport into passive transport

Correct Answer: It can add resistance, lowering apparent permeability especially for very lipophilic drugs

Q20. Which assay would you choose to rapidly screen passive membrane permeability for many compounds?

  • Caco-2 monolayer assay
  • In situ intestinal perfusion in rats
  • PAMPA high-throughput assay
  • Clinical human absorption study

Correct Answer: PAMPA high-throughput assay

Q21. If dQ/dt = 5 x 10^-7 mol/s, membrane area A = 1 cm² and donor concentration C0 = 1 x 10^-4 mol/cm³, what is Papp?

  • 5 x 10^-3 cm/s
  • 5 x 10^-6 cm/s
  • 5 x 10^-9 cm/s
  • 5 x 10^-2 cm/s

Correct Answer: 5 x 10^-3 cm/s

Q22. Which statement about Caco-2 cell monolayers is correct?

  • They lack tight junctions and only measure passive diffusion
  • They express many human intestinal transporters and enzymes
  • They only model hepatic clearance
  • They are derived from kidney tissue

Correct Answer: They express many human intestinal transporters and enzymes

Q23. Which change would likely increase a drug’s passive permeability across intestinal epithelium?

  • Increasing polar surface area
  • Increasing ionization at intestinal pH
  • Reducing hydrogen bond donors and acceptors
  • Increasing molecular weight dramatically

Correct Answer: Reducing hydrogen bond donors and acceptors

Q24. Efflux ratio (ER) in Caco-2 assays is calculated as:

  • ER = Papp (A→B) / Papp (B→A)
  • ER = Papp (B→A) / Papp (A→B)
  • ER = log P · Papp (A→B)
  • ER = dQ/dt · A

Correct Answer: ER = Papp (B→A) / Papp (A→B)

Q25. What is a typical Papp cutoff (order of magnitude) often used to classify high permeability in Caco-2 assays?

  • < 10^-8 cm/s
  • ~10^-6 to 10^-5 cm/s
  • > 1 cm/s
  • ~10^-2 mol/L

Correct Answer: ~10^-6 to 10^-5 cm/s

Q26. Which of the following best describes ‘transcellular passive diffusion’?

  • Movement through tight junctions between cells
  • Carrier-mediated transport across cell membranes
  • Diffusion through the cell lipid bilayer driven by concentration gradient
  • Endocytosis followed by exocytosis

Correct Answer: Diffusion through the cell lipid bilayer driven by concentration gradient

Q27. Which molecular feature often favors paracellular absorption?

  • High lipophilicity (high log P)
  • Small hydrophilic molecules with low lipophilicity
  • Large, highly lipophilic macromolecules
  • Strong binding to plasma proteins

Correct Answer: Small hydrophilic molecules with low lipophilicity

Q28. Which strategy can be used to overcome P-gp mediated efflux and improve oral permeability?

  • Decrease drug lipophilicity drastically
  • Co-administer P-gp inhibitors or modify structure to avoid recognition
  • Increase polar surface area
  • Reduce dose to sub-therapeutic levels

Correct Answer: Co-administer P-gp inhibitors or modify structure to avoid recognition

Q29. Which parameter is least relevant when interpreting in vitro permeability for predicting in vivo absorption?

  • Membrane integrity and tight junction status
  • Expression of transporters and enzymes
  • Assay temperature and pH
  • Color of the assay buffer

Correct Answer: Color of the assay buffer

Q30. When designing a permeability experiment, why is it important to measure donor concentration decline and acceptor accumulation?

  • To ensure the membrane dissolves during the assay
  • To calculate flux and Papp accurately and verify sink conditions
  • To increase the drug’s molecular weight
  • To validate chromatographic retention times only

Correct Answer: To calculate flux and Papp accurately and verify sink conditions

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