Introduction: The use of permeation enhancers in transdermal formulations is a key topic for B.Pharm students studying drug delivery. Permeation enhancers (chemical penetration enhancers) increase skin permeation by reversible modification of the stratum corneum structure, improving drug partitioning and diffusion. Important keywords include transdermal delivery, skin permeation, stratum corneum, penetration enhancers, flux, lag time, bioavailability, vehicles, surfactants, terpenes, fatty acids, azones, DMSO, propylene glycol, and safety. Understanding mechanisms, selection criteria, concentration effects, evaluation methods (Franz diffusion cell, tape stripping), and irritation/toxicity is essential for formulation development. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary barrier to drug permeation in transdermal delivery?
- Dermal blood vessels
- Stratum corneum
- Subcutaneous fat
- Sweat glands
Correct Answer: Stratum corneum
Q2. Which of the following best describes a permeation enhancer?
- A compound that permanently destroys skin lipids
- A chemical that transiently increases skin permeability to drugs
- A surfactant used only to solubilize drugs
- A polymeric film former for patches
Correct Answer: A chemical that transiently increases skin permeability to drugs
Q3. Which mechanism is commonly involved in the action of many chemical enhancers?
- Increase in dermal blood flow only
- Lipid bilayer disruption of the stratum corneum
- Permanent denaturation of skin proteins
- Blocking sweat gland openings
Correct Answer: Lipid bilayer disruption of the stratum corneum
Q4. Azone (laurocapram) primarily enhances permeation by:
- Acting as a strong surfactant to solubilize drugs
- Fluidizing intercellular lipids in the stratum corneum
- Increasing skin hydration via occlusion only
- Inhibiting metabolic enzymes in the skin
Correct Answer: Fluidizing intercellular lipids in the stratum corneum
Q5. Which solvent is known as a potent but potentially irritating permeation enhancer?
- Water
- Ethanol
- Propylene glycol
- Glycerin
Correct Answer: Ethanol
Q6. Terpenes (e.g., limonene) enhance permeation mainly by:
- Hydrating the viable epidermis exclusively
- Extracting lipids and disrupting lipid order
- Increasing molecular weight of drugs
- Inhibiting skin proteases
Correct Answer: Extracting lipids and disrupting lipid order
Q7. Which property of a drug favors transdermal delivery with the aid of a permeation enhancer?
- High molecular weight (>1000 Da)
- Low potency (high dose requirement)
- Balanced lipophilicity (log P 1–3) and low molecular weight
- Highly ionized at physiological pH
Correct Answer: Balanced lipophilicity (log P 1–3) and low molecular weight
Q8. Propylene glycol is used in transdermal systems mainly as:
- Aerosol propellant
- Permeation enhancer and co-solvent
- Polymeric matrix former
- Antimicrobial preservative only
Correct Answer: Permeation enhancer and co-solvent
Q9. Which in vitro method is widely used to evaluate skin permeation and enhancer effect?
- Disk diffusion assay
- Franz diffusion cell using excised skin
- Broth dilution method
- Centrifugation-spectroscopy assay
Correct Answer: Franz diffusion cell using excised skin
Q10. What is a common safety concern associated with strong chemical enhancers like DMSO?
- Permanent skin whitening
- Systemic toxicity due to excessive absorption
- Complete prevention of drug absorption
- Formation of rigid skin barrier
Correct Answer: Systemic toxicity due to excessive absorption
Q11. Tape stripping is primarily used to assess:
- Systemic drug levels after transdermal dosing
- Extent of stratum corneum removal and topical drug distribution
- Viscosity of topical formulations
- Buoyancy of patches in water
Correct Answer: Extent of stratum corneum removal and topical drug distribution
Q12. Fatty acids (e.g., oleic acid) enhance permeation by:
- Alkylating keratin
- Creating separate lipid domains and increasing fluidity
- Forming micelles that trap the drug
- Acting as pH buffers in the skin
Correct Answer: Creating separate lipid domains and increasing fluidity
Q13. Which parameter represents the steady-state permeation rate across skin?
- Lag time
- Flux (Jss)
- Permeability coefficient multiplied by molecular weight
- Skin thickness only
Correct Answer: Flux (Jss)
Q14. Combining physical methods (e.g., microneedles) with chemical enhancers can:
- Reduce permeation compared with either alone
- Synergistically increase drug delivery across skin
- Always cause irreversible skin damage
- Make enhancers inactive
Correct Answer: Synergistically increase drug delivery across skin
Q15. Which excipient class can act both as a vehicle and a permeation enhancer?
- Polymers like HPMC
- Alcohols and glycols (e.g., ethanol, propylene glycol)
- Inert fillers like talc
- Metallic salts
Correct Answer: Alcohols and glycols (e.g., ethanol, propylene glycol)
Q16. Reversibility of permeation enhancer action is important because:
- Permanent enhancement increases patient comfort
- Transient action reduces long-term skin damage and irritation
- It guarantees zero systemic absorption
- It prevents any change in drug solubility
Correct Answer: Transient action reduces long-term skin damage and irritation
Q17. Which assessment indicates increased drug partitioning into the skin caused by an enhancer?
- Decrease in steady-state flux
- Increased skin reservoir concentration measured after application
- Reduced drug solubility in the vehicle
- Shorter shelf-life of the formulation
Correct Answer: Increased skin reservoir concentration measured after application
Q18. Surfactants enhance permeation mainly by:
- Reducing skin pH drastically
- Solubilizing lipids and altering intercellular lipid organization
- Forming a physical barrier to drug diffusion
- Enzymatically cleaving keratin
Correct Answer: Solubilizing lipids and altering intercellular lipid organization
Q19. Which statement about enhancer concentration is generally true?
- Higher concentration always results in proportionally higher flux without safety issues
- There is often an optimum concentration beyond which irritation increases and benefits plateau
- Concentration has no impact on permeation efficacy
- Lower concentrations are always more effective than higher ones
Correct Answer: There is often an optimum concentration beyond which irritation increases and benefits plateau
Q20. Prodrug approach in transdermal delivery is used mainly to:
- Increase molecular weight to reduce absorption
- Enhance skin permeation by altering lipophilicity and enzymatic release in skin
- Make the drug more volatile
- Prevent skin metabolism permanently
Correct Answer: Enhance skin permeation by altering lipophilicity and enzymatic release in skin
Q21. Which of the following is NOT a desirable characteristic of a permeation enhancer?
- Non-toxic and non-irritant at effective dose
- Selective and reversible action on skin barrier
- Causes permanent lipid extraction and chronic skin damage
- Compatible with drug and formulation components
Correct Answer: Causes permanent lipid extraction and chronic skin damage
Q22. Measurement of lag time in a permeation study provides information about:
- Time taken to reach steady-state flux across skin
- Total amount of drug applied
- Vehicle evaporation rate only
- Systemic elimination half-life
Correct Answer: Time taken to reach steady-state flux across skin
Q23. Which enhancer is known for excellent penetration but limited clinical use due to irritation and odor?
- Glycerin
- DMSO (dimethyl sulfoxide)
- Polysorbate 80
- PEG 400
Correct Answer: DMSO (dimethyl sulfoxide)
Q24. In evaluating enhancers, the selectivity index compares:
- Enhancer melting point vs. drug melting point
- Enhancer permeation efficacy versus skin irritation potential
- Vehicle viscosity and patch adhesion
- Drug potency and tablet hardness
Correct Answer: Enhancer permeation efficacy versus skin irritation potential
Q25. Which class of enhancers often improves drug solubility in the vehicle and increases partitioning into skin?
- Hydrophilic polymers only
- Cosolvents like ethanol and propylene glycol
- Inert plasticizers
- Cross-linking agents
Correct Answer: Cosolvents like ethanol and propylene glycol
Q26. Which experimental model is most appropriate for initial screening of permeation enhancers?
- Human clinical trials immediately
- In vitro skin diffusion using excised human or animal skin
- Large-scale manufacturing stress tests
- Only in silico predictions without wet lab tests
Correct Answer: In vitro skin diffusion using excised human or animal skin
Q27. Occlusion influences enhancer performance by:
- Decreasing skin hydration
- Increasing skin hydration and often enhancing permeation
- Preventing enhancers from contacting skin
- Removing the stratum corneum instantly
Correct Answer: Increasing skin hydration and often enhancing permeation
Q28. Which analytical parameter is used to quantify skin permeation rate in Franz cell experiments?
- Permeability coefficient (Kp) and steady-state flux (Jss)
- pH of the receptor fluid only
- Color change of the skin sample
- Electrical conductivity of the donor solution
Correct Answer: Permeability coefficient (Kp) and steady-state flux (Jss)
Q29. For a hydrophilic drug, which enhancer strategy is most appropriate?
- Use of lipid-disrupting enhancers without any solvent
- Combination of hydration, iontophoresis or chemical enhancers that increase aqueous diffusion
- Increase molecular weight to reduce diffusion
- Avoid enhancers and rely only on occlusion
Correct Answer: Combination of hydration, iontophoresis or chemical enhancers that increase aqueous diffusion
Q30. Regulatory concerns for permeation enhancers focus mainly on:
- Manufacturing speed only
- Safety, irritation, systemic exposure and long-term skin effects
- Color and fragrance of the enhancer
- Market price regardless of safety
Correct Answer: Safety, irritation, systemic exposure and long-term skin effects
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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