Factors influencing dermal drug absorption MCQs With Answer

Dermal drug absorption depends on multiple physiological and formulation-related factors that determine percutaneous absorption and therapeutic efficacy. For B. Pharm students, understanding skin permeability, the role of the stratum corneum barrier, and key determinants—drug physicochemical properties (molecular size, lipophilicity/logP, ionization), concentration gradient, vehicle and formulation, occlusion, penetration enhancers, skin hydration, temperature, blood flow, application site, and skin metabolism—is essential for designing topical and transdermal systems. Concepts such as Fick’s laws, permeability coefficient, lag time, appendageal pathways, and in vitro models (Franz diffusion cell, tape-stripping) link theory to practice. Mastering these factors helps optimize bioavailability and minimize local/systemic side effects. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which layer of the skin is the primary barrier to dermal drug absorption?

• Dermis
• Stratum corneum
• Hypodermis
• Basal cell layer

Correct Answer: Stratum corneum

Q2. According to Fick’s first law, which factor directly increases steady-state flux of a drug across skin?

• Decreasing concentration gradient
• Increasing diffusion path length
• Increasing permeability coefficient
• Increasing lag time

Correct Answer: Increasing permeability coefficient

Q3. Which physicochemical property most favors passive transdermal permeation?

• Very large molecular weight (>1000 Da)
• High aqueous solubility only
• Moderate lipophilicity (logP ~1–3)
• Strong ionic charge at physiological pH

Correct Answer: Moderate lipophilicity (logP ~1–3)

Q4. How does occlusion affect dermal drug absorption?

• Reduces permeation by blocking the vehicle
• Decreases skin hydration and reduces flux
• Increases stratum corneum hydration and increases flux
• Neutral effect on permeability

Correct Answer: Increases stratum corneum hydration and increases flux

Q5. Which route provides a major appendageal pathway for drug penetration?

• Intercellular lipid route through corneocytes
• Transcellular keratin route
• Hair follicles and sweat glands
• Subcutaneous fat channels

Correct Answer: Hair follicles and sweat glands

Q6. Which of the following drug characteristics decreases skin permeability most strongly?

• Low molecular weight
• High lipophilicity
• High polarity and ionization
• Neutral charge

Correct Answer: High polarity and ionization

Q7. What is the primary effect of a penetration enhancer like ethanol when added to a topical formulation?

• Inhibits stratum corneum enzymes
• Increases skin blood flow only
• Alters lipid structure to increase permeability
• Forms a film to prevent drug loss

Correct Answer: Alters lipid structure to increase permeability

Q8. Which experimental model is commonly used for in vitro measurement of transdermal flux?

• Diffusion bonding chamber
• Franz diffusion cell
• Rotating basket apparatus
• Disintegration tester

Correct Answer: Franz diffusion cell

Q9. How does increasing temperature at the application site generally affect dermal absorption?

• Decreases diffusion coefficient
• Has no effect on permeability
• Increases molecular mobility and flux
• Increases lag time

Correct Answer: Increases molecular mobility and flux

Q10. Which parameter represents the time required to reach steady-state permeation?

• Permeability coefficient (Kp)
• Steady-state flux (Jss)
• Lag time (tlag)
• Partition coefficient (K)

Correct Answer: Lag time (tlag)

Q11. Which formulation factor can increase drug thermodynamic activity and drive higher skin uptake?

• Using a saturated solution of the drug
• Lowering concentration below solubility
• Adding excessive inert fillers
• Applying minimal dose

Correct Answer: Using a saturated solution of the drug

Q12. Which site on the body typically has the highest transdermal permeability?

• Palm of the hand
• Soles of the feet
• Scrotal or genital skin
• Forearm

Correct Answer: Scrotal or genital skin

Q13. In the permeability coefficient equation Kp = (KD)/h, what does D represent?

• Partition coefficient between vehicle and skin
• Diffusion coefficient in the skin
• Drug dose applied
• Thickness of the formulation film

Correct Answer: Diffusion coefficient in the skin

Q14. Which skin condition would likely increase systemic absorption of a topical drug?

• Intact healthy stratum corneum
• Hyperkeratosis
• Eczema with barrier disruption
• Thick callused skin

Correct Answer: Eczema with barrier disruption

Q15. How does drug ionization according to pH-partition theory affect dermal absorption?

• Ionized forms cross lipid barriers more easily
• Unionized forms cross the lipid-rich stratum corneum more readily
• Ionization has no impact on permeation
• Only ionized drugs penetrate via appendageal routes

Correct Answer: Unionized forms cross the lipid-rich stratum corneum more readily

Q16. Which analytical technique is used to study stratum corneum removal and drug distribution in tape-stripping studies?

• High performance liquid chromatography (HPLC)
• Thermogravimetric analysis
• Mass spectrometry only without separation
• Microscopy without quantitation

Correct Answer: High performance liquid chromatography (HPLC)

Q17. Which statement about vehicle effects is correct?

• Oily vehicles always decrease skin penetration
• Water-based vehicles cannot enhance lipophilic drug delivery
• Vehicle composition can modify partitioning and thermodynamic activity
• Vehicle has no role once drug contacts skin

Correct Answer: Vehicle composition can modify partitioning and thermodynamic activity

Q18. Which of the following techniques actively enhances transdermal delivery using electric current?

• Microneedle arrays
• Iontophoresis
• Sonophoresis
• Prodrug formation

Correct Answer: Iontophoresis

Q19. Which enzymatic activity in the skin can influence a topically applied prodrug?

• Gastric peptidases
• Skin esterases and CYP enzymes
• Pankreatic lipase
• Renal dehydrogenases

Correct Answer: Skin esterases and CYP enzymes

Q20. What is the likely effect of increasing the contact area of application while keeping dose constant?

• Decreases flux per unit area
• Increases total absorbed dose but may decrease local flux per area
• No change in absorption
• Eliminates lag time

Correct Answer: Increases total absorbed dose but may decrease local flux per area

Q21. Which characteristic of a penetration enhancer would minimize skin irritation while improving permeation?

• Strong surfactant that solubilizes keratin extensively
• Highly reactive chemical that denatures proteins
• Mild lipid-disordering agent with reversible effects
• Strong acid to break intercellular lipids

Correct Answer: Mild lipid-disordering agent with reversible effects

Q22. In transdermal system design, what is the function of a rate-controlling membrane?

• To increase thermodynamic activity of the drug
• To control and maintain a constant release rate to skin
• To act as a skin penetration enhancer
• To rapidly deplete drug reservoir

Correct Answer: To control and maintain a constant release rate to skin

Q23. Which in vivo factor can reduce dermal drug absorption compared to in vitro results?

• Constant receiver fluid in vitro
• Higher skin blood flow in vivo
• Continuous removal by systemic circulation in vivo
• Absence of metabolism in vivo

Correct Answer: Continuous removal by systemic circulation in vivo

Q24. Which molecular weight cutoff is often cited as limiting for effective passive skin permeation?

• < 50 Da
• ~100–200 Da
• ~500 Da
• >1000 Da

Correct Answer: ~500 Da

Q25. Why are prodrugs used in topical/transdermal delivery?

• To permanently bind drug to skin proteins
• To worsen skin irritation deliberately
• To transiently improve lipophilicity or permeability and be converted in skin
• To avoid enzymatic conversion in skin

Correct Answer: To transiently improve lipophilicity or permeability and be converted in skin

Q26. Which measurement describes drug affinity for skin lipids relative to vehicle?

• Partition coefficient (K)
• Diffusion coefficient (D)
• Permeability coefficient (Kp)
• Lag time (tlag)

Correct Answer: Partition coefficient (K)

Q27. What is the effect of skin hydration on diffusion coefficient D in the stratum corneum?

• Hydration decreases D by tightening lipids
• Hydration increases D by plasticizing the stratum corneum
• Hydration eliminates partitioning
• Hydration converts drug to non-absorbable form

Correct Answer: Hydration increases D by plasticizing the stratum corneum

Q28. Which formulation approach can reduce systemic exposure while enhancing local skin concentration?

• Highly occlusive formulation over large area
• Use of microneedles without drug reservoir
• Topical liposomal or microemulsion designed for skin deposition
• Highly volatile solvent for rapid systemic uptake

Correct Answer: Topical liposomal or microemulsion designed for skin deposition

Q29. Which of the following enhances follicular targeting of drugs?

• Use of very large particles >10 µm
• Inclusion of hair removal prior to application
• Formulation as nanoparticle or oily vehicle for follicle penetration
• Applying on desensitized skin

Correct Answer: Formulation as nanoparticle or oily vehicle for follicle penetration

Q30. What is a major limitation when interpreting in vitro skin permeation data for human risk assessment?

• In vitro systems replicate systemic clearance accurately
• In vitro models always overpredict in vivo absorption
• Differences in skin source, integrity, and absence of blood flow can limit extrapolation
• In vitro always accounts for skin metabolism

Correct Answer: Differences in skin source, integrity, and absence of blood flow can limit extrapolation

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