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

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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