Understanding factors influencing dermal penetration is essential for B.Pharm students, as skin permeability determines topical drug delivery, transdermal absorption, and therapeutic efficacy. Key concepts include the stratum corneum barrier, molecular size and shape, lipophilicity (log P), partition and diffusion coefficients, vehicle or formulation effects, skin hydration, occlusion, chemical penetration enhancers, skin metabolism, pH, and regional blood flow. Experimental variables such as dose, contact time, and skin condition also alter permeation. These topics tie into pharmacokinetics, regulatory considerations, formulation stability, clinical translation, and in vitro/in vivo correlation studies. A clear grasp of mechanisms, experimental methods, and data interpretation is vital for rational topical formulation. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which skin layer acts as the primary barrier to dermal penetration?
- Epidermis
- Dermis
- Stratum corneum
- Sebaceous glands
Correct Answer: Stratum corneum
Q2. Which molecular weight range is generally most favorable for passive dermal penetration?
- <500 Da
- 500–1000 Da
- <200 Da
- >1000 Da
Correct Answer: <500 Da
Q3. Which physicochemical property is most critical in determining a drug’s ability to partition into the skin lipids?
- Molecular weight
- Lipophilicity (log P)
- pKa
- Melting point
Correct Answer: Lipophilicity (log P)
Q4. According to Fick’s first law, steady-state flux through skin is primarily determined by which factors?
- Partition coefficient and skin surface area
- Diffusion coefficient and concentration gradient
- pH and ionization only
- Vehicle viscosity and application method
Correct Answer: Diffusion coefficient and concentration gradient
Q5. Which expression best represents the permeability coefficient (Kp) for dermal transport?
- Kp = (D × K) / h
- Kp = D × h × K
- Kp = h / (D × K)
- Kp = D / (K × h)
Correct Answer: Kp = (D × K) / h
Q6. The lag time (tlag) for a drug diffusing through a homogeneous membrane is proportional to which of the following?
- h / D
- h² / (6D)
- D / h²
- 6D / h²
Correct Answer: h² / (6D)
Q7. Which type of additives commonly enhance dermal penetration by disrupting stratum corneum lipids?
- Humectants only
- Preservatives
- Chemical penetration enhancers (e.g., ethanol, DMSO, azone)
- Colorants
Correct Answer: Chemical penetration enhancers (e.g., ethanol, DMSO, azone)
Q8. How does the formulation vehicle influence dermal absorption?
- It only affects the drug’s chemical stability, not absorption
- It modifies thermodynamic activity and drug partitioning into skin
- Vehicle has no role once the drug is applied
- It only changes the pH of the skin surface
Correct Answer: It modifies thermodynamic activity and drug partitioning into skin
Q9. What is the effect of increased stratum corneum hydration on drug permeation?
- Decreases permeability by tightening lipid lamellae
- Increases permeability by swelling the corneocytes and disrupting lipids
- No effect on permeability
- Only affects appendageal routes, not intercellular pathways
Correct Answer: Increases permeability by swelling the corneocytes and disrupting lipids
Q10. Occlusion (covering a topical application) typically causes which change relevant to dermal penetration?
- Decreased hydration and reduced flux
- Increased skin hydration and enhanced flux
- Reduced thermodynamic activity of the drug
- Immediate systemic elimination
Correct Answer: Increased skin hydration and enhanced flux
Q11. Which route provides a fast pathway for some compounds, partially bypassing the stratum corneum?
- Transcellular route
- Intercellular lipid route
- Appendageal (hair follicle and sweat gland) route
- Vascular route
Correct Answer: Appendageal (hair follicle and sweat gland) route
Q12. For passive skin permeation, which logP (octanol/water) range is often considered optimal?
- <0 (very hydrophilic)
- 1–3
- 4–6 (very lipophilic)
- >6
Correct Answer: 1–3
Q13. How does ionization (pKa) of a drug affect dermal absorption?
- Ionic species always penetrate better than unionized
- Unionized species penetrate the lipid-rich stratum corneum more readily
- pKa is irrelevant for skin permeation
- Only cationic drugs can penetrate skin
Correct Answer: Unionized species penetrate the lipid-rich stratum corneum more readily
Q14. What is the general relationship between drug melting point and dermal penetration?
- Higher melting point generally increases skin penetration
- Lower melting point often correlates with better skin penetration
- Melting point has no influence on skin absorption
- Only crystalline drugs penetrate skin well
Correct Answer: Lower melting point often correlates with better skin penetration
Q15. Cutaneous metabolism by skin enzymes primarily affects dermal drug delivery by:
- Enhancing systemic bioavailability always
- Inactivating or biotransforming drugs, reducing active systemic exposure
- Preventing any absorption through the epidermis
- Only affecting peptide drugs, not small molecules
Correct Answer: Inactivating or biotransforming drugs, reducing active systemic exposure
Q16. Which experimental apparatus is commonly used for in vitro measurement of skin permeation?
- High-performance liquid chromatography (HPLC)
- Franz diffusion cell with excised skin
- Mass spectrometer alone
- Patch clamp
Correct Answer: Franz diffusion cell with excised skin
Q17. Which parameter denotes steady-state flux in dermal permeation studies?
- Kp
- tlag
- Jss
- D
Correct Answer: Jss
Q18. What happens to dermal flux when the thermodynamic activity of the drug in the vehicle increases (up to saturation)?
- Flux is independent of thermodynamic activity
- Flux decreases with increased thermodynamic activity
- Flux increases proportionally with thermodynamic activity until saturation
- Flux stops immediately due to vehicle evaporation
Correct Answer: Flux increases proportionally with thermodynamic activity until saturation
Q19. How does reducing particle size (e.g., nanoparticles) of a topical formulation generally affect dermal delivery?
- Decreased follicular uptake and reduced penetration
- No impact on skin uptake
- Increased penetration and enhanced follicular targeting
- Always causes systemic toxicity
Correct Answer: Increased penetration and enhanced follicular targeting
Q20. When designing a transdermal patch, occlusion provided by the patch membrane primarily produces which effect?
- Reduced drug flux due to membrane barrier
- Increased skin hydration and enhanced percutaneous absorption
- Immediate degradation of the drug
- No effect on skin conditions
Correct Answer: Increased skin hydration and enhanced percutaneous absorption
Q21. Which of the following is a classic lipid-disordering penetration enhancer used in topical formulations?
- Sorbitol
- Oleic acid
- Sodium chloride
- Ascorbic acid
Correct Answer: Oleic acid
Q22. Which technique specifically samples stratum corneum layers to quantify local drug concentration?
- Tape-stripping
- Skin biopsy only
- Whole blood sampling
- Urine assay
Correct Answer: Tape-stripping
Q23. Which anatomical site generally exhibits the highest permeability to topical drugs?
- Forearm
- Scalp
- Plantar foot
- Genital/scrotal skin
Correct Answer: Genital/scrotal skin
Q24. How does an increase in temperature affect dermal permeation rates?
- Temperature has no effect on permeation
- Increased temperature reduces diffusion coefficient
- Increased temperature typically increases diffusion coefficient and flux
- Only changes pH, not permeation
Correct Answer: Increased temperature typically increases diffusion coefficient and flux
Q25. Which molecular property tends to reduce passive transdermal permeation?
- Low polar surface area
- High lipophilicity within optimal range
- High polar surface area and high hydrogen-bonding capacity
- Low molecular weight
Correct Answer: High polar surface area and high hydrogen-bonding capacity
Q26. In most topical systems, what is commonly the rate-controlling step for drug delivery to systemic circulation?
- Release from the transdermal backing layer
- Diffusion through the stratum corneum
- Renal clearance
- Gastrointestinal absorption
Correct Answer: Diffusion through the stratum corneum
Q27. Which OECD guideline is relevant for in vitro skin absorption studies?
- OECD 305
- OECD 428
- ICH Q3A
- FDA 21 CFR Part 11
Correct Answer: OECD 428
Q28. Which formulation strategy can increase the thermodynamic activity of a drug at the skin surface after application?
- Using a non-volatile solvent that never evaporates
- Incorporating a volatile cosolvent (e.g., ethanol) that evaporates and increases drug activity
- Adding excessive emulsifiers to reduce activity
- Applying vehicle at subthermodynamic levels
Correct Answer: Incorporating a volatile cosolvent (e.g., ethanol) that evaporates and increases drug activity
Q29. How do surfactants in topical formulations commonly affect dermal penetration?
- They only stabilize emulsions and never affect skin lipids
- They can act as penetration enhancers by disrupting lipid structure
- They always reduce permeation by forming micelles
- They solely modify pH without lipid interaction
Correct Answer: They can act as penetration enhancers by disrupting lipid structure
Q30. What is the principal safety concern when dermal penetration is unintentionally increased?
- Enhanced local color change only
- Increased systemic exposure and potential systemic toxicity
- Guaranteed therapeutic benefit without risk
- Reduced transdermal flux
Correct Answer: Increased systemic exposure and potential systemic toxicity

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.
Mail- Sachin@pharmacyfreak.com

