PHA 338 - Transdermal L16

What are the major layers of the skin?

Epidermis, dermis, and subcutaneous tissue (hypodermis).

What is the primary barrier and rate-limiting step for percutaneous absorption?

The stratum corneum.

Describe the stratum corneum.

The outer epidermal layer composed of dead keratinized cells (corneocytes) embedded in a lipid matrix.

Describe the dermis.

A 3–5 mm thick connective tissue layer containing collagen, blood vessels, nerves, sweat glands, and hair follicles.

What are Langerhans cells?

The major antigen-presenting cells of the skin.

What is the function of sebaceous glands?

They secrete sebum, which lubricates the skin and helps maintain a surface pH of about 5.

What is topical delivery?

Application of a drug to the skin for local effects.

What is transdermal delivery?

Delivery of a drug through the skin into systemic circulation.

What are examples of conventional dermatological dosage forms?

Gels, lotions, creams, and ointments.

What are the advantages of transdermal delivery?

Avoids first-pass metabolism, provides sustained delivery, is noninvasive, allows self-administration, allows therapy termination by patch removal, reduces adverse effects, and permits multiday therapy.

What are the limitations of passive transdermal delivery?

Works mainly for potent, low-dose, moderately lipophilic, uncharged drugs with low molecular weight and wide therapeutic windows.

Why are potent drugs preferred for transdermal delivery?

Only limited amounts of drug can cross the skin.

Why are low-dose drugs preferred for transdermal delivery?

The skin barrier limits drug delivery.

What type of drug charge is preferred for passive transdermal delivery?

Uncharged.

What lipophilicity is preferred for passive transdermal delivery?

Moderately lipophilic.

What is the ideal log P range for passive transdermal delivery?

1 to 3.5.

What molecular weight is preferred for passive transdermal delivery?

Less than 500 Da.

What daily dose is preferred for passive transdermal delivery?

Less than 10 mg/day.

What solubility is preferred for passive transdermal delivery?

Greater than 100 μg/mL.

What flux is considered ideal for a transdermal drug?

Approximately 1 mg/cm²/day.

What factors affect percutaneous absorption?

Drug concentration, solubility, partition coefficient, surface area, skin hydration, temperature, application site, penetration enhancers, age, race, and molecular weight.

How does skin hydration affect absorption?

Increased hydration generally increases absorption.

How does temperature affect absorption?

Increased temperature generally increases absorption.

How does surface area affect absorption?

Larger surface area generally increases drug delivery.

Why is the site of application important?

Skin thickness and permeability vary among body sites.

What is a Franz diffusion cell used for?

In vitro evaluation of transdermal drug delivery through skin.

What skin types are commonly used in Franz cell studies?

Human or porcine skin.

What are the two major types of transdermal systems?

Drug-in-adhesive (matrix) systems and reservoir systems.

What is a drug-in-adhesive (DIA) patch?

A patch in which the drug is incorporated directly into the adhesive layer.

What are common adhesive types used in DIA patches?

Acrylate, silicone, and polyisobutylene.

What is a reservoir patch?

A patch containing a drug reservoir separated from the skin by a rate-controlling membrane.

What are the components of a reservoir patch?

Backing, drug reservoir, control membrane, adhesive layer, and protective peel strip.

What controls drug release in a reservoir patch?

The control membrane.

What major problem is associated with reservoir patches?

Leakage.

Which drug had deaths and recalls associated with reservoir patch leakage?

Fentanyl.

Why are some reservoir patches reformulated into matrix patches?

To reduce leakage problems.

What is lag time in transdermal delivery?

The delay between patch application and measurable systemic drug delivery or effect.

Why does lag time occur?

The drug must diffuse through the patch and skin before reaching systemic circulation.

Why may fentanyl patch patients need oral narcotics initially?

Because the patch may require a day or two to reach full effect.

What is the first transdermal product marketed?

Transderm-Scop (scopolamine).

Why is nitroglycerin a good transdermal candidate?

It is potent, has a short half-life, and undergoes extensive first-pass metabolism.

What are nicotine patches used for?

Smoking cessation.

What is the standard nicotine patch schedule?

21 mg/day for 6 weeks, then 14 mg/day for 2 weeks, then 7 mg/day for 2 weeks.

How should nicotine patches be applied?

To a clean, dry, nonhairy area with daily site rotation.

What skin reaction may occur with nicotine patches?

Mild, short-lived erythema.

What should be done in case of nicotine patch overdose?

Remove the patch and flush the area with water; do not use soap.

What can patients do if nicotine patches cause vivid dreams?

Remove the patch at bedtime.

Why must nicotine patches be disposed of properly?

Used patches still contain nicotine.

How should fentanyl patches be applied?

To a dry, flat area; hair may be clipped but not shaved.

What should be avoided while wearing fentanyl patches?

Heating pads and other external heat sources.

Why should heat be avoided with transdermal patches?

Heat can increase drug absorption and cause toxicity.

How is a scopolamine patch used?

Apply behind the ear at least 4 hours before needed and wear for up to 3 days.

What should be done before an MRI when wearing a patch?

Remove the patch.

What body sites are commonly used for patch placement?

Upper arm, back, buttock, and flank.

What body sites should be avoided for patch placement?

Hairy, broken, irritated, or damaged skin.

Why should patch application sites be rotated?

To reduce irritation and improve adhesion.

What should patients avoid touching when applying a patch?

The adhesive surface.

What should be done before applying a new patch?

Remove the old patch.

Should patches be cut?

No.

Should multiple patches be applied to make up for a missed dose?

No.

Why should patches be disposed of carefully?

Residual drug may cause abuse, poisoning, or environmental hazards.

What is crystallization in a transdermal patch?

Formation of drug crystals within the patch matrix over time.

What problems can crystallization cause?

Reduced flux, instability, irritation, and poor appearance.

Which patch was withdrawn because of crystallization problems?

Rotigotine (Neupro).

What polymer was discussed as a crystallization inhibitor?

Polyvinylpyrrolidone (PVP).

What is adhesive failure?

Loss of proper patch adhesion to the skin.

Why is adhesive failure important?

It can result in underdosing, increased cost, and unintended drug exposure.

What is dose dumping?

Rapid release of excessive drug from a dosage form.

What are examples of safety issues with transdermal patches?

Increased absorption from heat, dose dumping, leakage, accidental ingestion, misuse, and MRI burns.

What enhancement technologies can increase drug delivery through skin?

Chemical enhancers, iontophoresis, skin microporation, microneedles, electroporation, sonophoresis, and microdermabrasion.

What is iontophoresis?

Use of electrical current to enhance drug transport through skin.

What is electroporation?

Use of short electrical pulses to increase skin permeability.

What is sonophoresis?

Use of ultrasound to enhance transdermal drug delivery.

What is skin microporation?

Creation of microscopic pores in the skin to improve drug penetration.

What are microneedles?

Microscopic needles that create channels through the stratum corneum.

What is microdermabrasion?

Mechanical disruption of the outer skin layer to improve drug penetration.

What are chemical penetration enhancers?

Chemicals that increase drug movement through the skin.

What sulfoxide penetration enhancer was discussed?

DMSO.

What alcohol penetration enhancer was discussed?

Ethanol.

What glycol penetration enhancer was discussed?

Propylene glycol.

What surfactant penetration enhancer was discussed?

Polysorbate 80.

What terpene penetration enhancer was discussed?

Menthol.

What fatty acid penetration enhancers were discussed?

Oleic acid and isopropyl myristate (IPM).

What does IPM stand for?

Isopropyl myristate.

What does PSA stand for in transdermal formulations?

Pressure-sensitive adhesive.

What is the most important barrier to percutaneous absorption?

The stratum corneum.

What are the key counseling points for transdermal patches?

Apply to clean, dry, intact skin; rotate sites; avoid heat; remove old patch before applying a new one; do not cut patches; dispose of patches properly.

What are the three main categories of enhancement technologies discussed in class?

Chemical enhancers, skin microporation, and iontophoresis.

What are examples of additional enhancement technologies?

Electroporation, sonophoresis, microdermabrasion, microneedles, powder injection, spray mist, prodrugs, eutectic systems, magnetophoresis, and cold plasma.

Stratum corneum

rate-limiting barrier

Ideal transdermal drug

Log P 1–3.5, MW < 500 Da, dose < 10 mg/day, potent, uncharged