Permeation of drugs through skin and influencing factors MCQs With Answer

Introduction

Permeation of drugs through skin is a key topic in transdermal delivery and topical therapy for B. Pharm students. Understanding mechanisms—stratum corneum barrier, diffusion, partitioning, and skin appendage pathways—helps predict drug flux, permeability coefficient, lag time, and bioavailability. Influencing factors include molecular weight, lipophilicity (log P), ionization, vehicle composition, skin hydration, occlusion, chemical enhancers, pH, and skin metabolism. Experimental tools like Franz diffusion cells and in vivo studies validate formulation performance. Mastery of these concepts aids rational design of transdermal systems, selection of penetration enhancers, and interpretation of permeation data. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which skin layer is the primary barrier to drug permeation?

  • Dermis
  • Stratum corneum
  • Viable epidermis
  • Subcutaneous fat

Correct Answer: Stratum corneum

Q2. According to Fick’s first law, steady-state flux (J) across the skin is directly proportional to which parameter?

  • Partition coefficient only
  • Concentration gradient
  • Molecular weight squared
  • Skin thickness only

Correct Answer: Concentration gradient

Q3. Which property most strongly favors transdermal permeation of a drug?

  • Very high molecular weight (>1000 Da)
  • High lipophilicity with moderate aqueous solubility (log P ~1–3)
  • Very high aqueous solubility and zero lipophilicity
  • Permanent positive charge

Correct Answer: High lipophilicity with moderate aqueous solubility (log P ~1–3)

Q4. What effect does occlusion generally have on drug permeation through skin?

  • Decreases hydration and reduces permeation
  • Increases skin hydration and enhances permeation
  • Neutral effect on stratum corneum
  • Causes immediate skin metabolism of the drug

Correct Answer: Increases skin hydration and enhances permeation

Q5. Which of the following is a common chemical penetration enhancer used in topical formulations?

  • Sodium chloride
  • Propylene glycol
  • Starch
  • Cellulose acetate

Correct Answer: Propylene glycol

Q6. Lag time in skin permeation experiments represents:

  • The time to reach steady-state flux
  • Total duration of the experiment
  • Time after which drug degradation occurs
  • Time taken for skin irritation to appear

Correct Answer: The time to reach steady-state flux

Q7. Which pathway allows preferential permeation of hydrophilic molecules through skin?

  • Intercellular lipid pathway
  • Transcellular pathway through corneocytes
  • Appendageal (hair follicle and sweat gland) pathway
  • Subcutaneous adipose pathway

Correct Answer: Appendageal (hair follicle and sweat gland) pathway

Q8. The permeability coefficient (Kp) is best described as:

  • Flux divided by concentration difference across the membrane
  • Product of molecular weight and log P
  • Time required for drug absorption
  • Concentration of drug in the vehicle

Correct Answer: Flux divided by concentration difference across the membrane

Q9. How does increasing a drug’s degree of ionization at skin pH affect permeation?

  • Ionized form increases lipophilicity and permeation
  • Ionized form decreases lipophilicity and reduces permeation
  • No effect; ionization does not influence permeation
  • Always increases permeation regardless of pH

Correct Answer: Ionized form decreases lipophilicity and reduces permeation

Q10. Which experimental apparatus is most commonly used for in vitro skin permeation studies?

  • Petri dish diffusion
  • Franz diffusion cell
  • High-performance liquid chromatography
  • UV–Vis spectrophotometer

Correct Answer: Franz diffusion cell

Q11. Which factor does NOT significantly influence skin permeation?

  • Vehicle composition
  • Drug melting point
  • Ambient temperature
  • Skin condition (intact vs damaged)

Correct Answer: Drug melting point

Q12. Azone (laurocapram) acts as a penetration enhancer primarily by:

  • Protein denaturation in dermis
  • Disrupting intercellular lipid packing in stratum corneum
  • Increasing transdermal blood flow
  • Forming a drug reservoir in subcutaneous fat

Correct Answer: Disrupting intercellular lipid packing in stratum corneum

Q13. Which drug attribute typically reduces transdermal absorption?

  • Molecular weight < 500 Da
  • High hydrogen-bonding capacity
  • Moderate lipophilicity
  • Neutral uncharged state at skin pH

Correct Answer: High hydrogen-bonding capacity

Q14. Which statement about transdermal patches is correct?

  • They always deliver drugs at a constant zero-order rate without design considerations
  • Rate-controlling membrane or matrix design influences drug flux
  • Occlusive backing decreases drug permeation
  • Patches cannot use chemical enhancers

Correct Answer: Rate-controlling membrane or matrix design influences drug flux

Q15. Skin metabolism can affect topical drug therapy by:

  • Never metabolizing drugs because skin lacks enzymes
  • Activating prodrugs or inactivating parent drugs via cutaneous enzymes
  • Only causing photodegradation but no enzymatic change
  • Removing drugs solely via sweat excretion

Correct Answer: Activating prodrugs or inactivating parent drugs via cutaneous enzymes

Q16. Which measurement indicates the amount of drug crossing per unit area per unit time?

  • Lag time
  • Flux (J)
  • Partition coefficient
  • Vehicle viscosity

Correct Answer: Flux (J)

Q17. Increasing skin temperature generally results in:

  • Decreased diffusion coefficient and reduced permeation
  • Increased diffusion coefficient and enhanced permeation
  • Complete denaturation of skin lipids blocking permeation
  • No change in transdermal flux

Correct Answer: Increased diffusion coefficient and enhanced permeation

Q18. Which vehicle property promotes drug release and subsequent skin uptake?

  • Strong drug–vehicle binding that prevents partitioning
  • High solvent evaporation leaving drug on skin surface
  • Optimal solubility of drug in vehicle with good partitioning into skin
  • Extremely viscous vehicle that traps drug permanently

Correct Answer: Optimal solubility of drug in vehicle with good partitioning into skin

Q19. Which molecular weight cutoff is often cited as a practical limit for passive transdermal delivery?

  • < 100 Da
  • < 500 Da
  • < 2000 Da
  • No limit; any size can passively permeate equally

Correct Answer: < 500 Da

Q20. Which of the following is a physical enhancement technique for increasing skin permeation?

  • Using ethanol as solvent
  • Iontophoresis
  • Adding propylene glycol
  • Applying occlusive film

Correct Answer: Iontophoresis

Q21. Permeation enhancers that extract lipids from stratum corneum mainly act by:

  • Increasing blood flow in dermis
  • Removing intercellular lipids to increase diffusion pathways
  • Cross-linking corneocyte proteins
  • Neutralizing drug charge

Correct Answer: Removing intercellular lipids to increase diffusion pathways

Q22. Which parameter is directly influenced by the drug–vehicle partition coefficient (K)?

  • Skin thickness
  • Extent of drug partition into stratum corneum
  • pH of the skin surface
  • Number of hair follicles

Correct Answer: Extent of drug partition into stratum corneum

Q23. In a Franz cell experiment, using human cadaver skin instead of animal skin primarily improves:

  • Reproducibility only, but not relevance
  • Clinical relevance of permeation data to humans
  • Analytical sensitivity of drug assay
  • Rate of drug degradation in receiver medium

Correct Answer: Clinical relevance of permeation data to humans

Q24. Which effect is associated with supersaturated topical formulations?

  • Decreased thermodynamic activity and lower flux
  • Increased thermodynamic activity and enhanced flux
  • Immediate crystallization that prevents absorption always
  • Lower skin irritation due to dilution

Correct Answer: Increased thermodynamic activity and enhanced flux

Q25. Which is a limitation of passive transdermal delivery?

  • High permeability for large polar molecules
  • Limited to drugs with suitable potency and physicochemical properties
  • Cannot provide controlled release
  • Never influenced by formulation factors

Correct Answer: Limited to drugs with suitable potency and physicochemical properties

Q26. Which skin appendage contributes disproportionately to permeation despite occupying small surface area?

  • Stratum corneum
  • Hair follicles
  • Dermal capillaries
  • Keratinocytes

Correct Answer: Hair follicles

Q27. Which term describes the drug’s tendency to move from vehicle into skin?

  • Evaporation rate
  • Partitioning
  • Viscosity
  • Melting point

Correct Answer: Partitioning

Q28. Which analytical endpoint is commonly used to determine steady-state flux from permeation data?

  • Slope of cumulative amount versus square root of time
  • Intercept of cumulative amount axis only
  • Slope of cumulative amount versus time during linear region
  • Maximum concentration in donor compartment

Correct Answer: Slope of cumulative amount versus time during linear region

Q29. Enhancers that increase drug solubility in the stratum corneum most likely act by:

  • Increasing aqueous solubility in receiver medium
  • Improving partitioning of drug into skin lipids
  • Reducing blood flow in dermis
  • Blocking hair follicle openings

Correct Answer: Improving partitioning of drug into skin lipids

Q30. Which approach reduces systemic exposure while maximizing local skin concentration?

  • Designing a rapidly permeating systemic prodrug
  • Using targeted topical formulations with limited transdermal flux
  • Increasing vehicle volatility to evaporate drug
  • Applying multiple layers of patches to increase flux

Correct Answer: Using targeted topical formulations with limited transdermal flux

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