Transdermal Drug Delivery Systems

Practice questions covering the anatomy of the skin, components and mechanisms of transdermal patches, and the factors affecting drug permeation.

What are the three main layers of the skin?

Epidermis, dermis, and subcutaneous tissue.

What is the function of the epidermis?

As the outermost layer, it provides a waterproof barrier.

What are the two specific routes mentioned for drug permeation through the epidermis?

Intercellular and Transcellular routes.

Which skin preparation type includes dermal and transdermal patches?

Device.

What is the definition of a transdermal patch?

A medicated adhesive patch that delivers drugs through the skin and into the bloodstream.

What is the primary mechanism of action for drug delivery in transdermal patches?

Passive diffusion based on Fick’s first law of diffusion.

What are the five essential components of a Transdermal Therapeutic System (TTS)?

Backing film, drug reservoir, membrane, adhesive, and liner.

What clinical condition are Glyceryl Trinitrate patches used to treat?

Ischemic Heart Disease.

Match the drug Fentanyl and Rivastigmine to their respective transdermal uses.

Fentanyl is used for pain management; Rivastigmine is used for dementia.

State the formula for Fick’s first law of Diffusion as applied to drug permeation.

$$\frac{Dm}{Dt} = \frac{D \times A \times (C_d - C_r)}{X}$$

Define the variable $D$ in Fick’s law and specify how it can be increased in TDD.

$D$ is the diffusion coefficient (speed). It can be increased using permeation enhancers (like PG) or physical methods like microneedling

How does the surface area ($A$) affect the rate of diffusion in transdermal delivery?

Directly proportional: a bigger surface area leads to more particles moving through, which can be achieved by increasing patch size.

Which skin sites are recommended for better permeation due to lower thickness ($X$)?

Upper chest, lower abdomen, and inner arm (lower thickness due to nature of stratum corneum and hair density)

How do inflammation and calluses contrast in their effect on skin permeability?

Inflamed skin increases permeability, while corn or calluses decrease permeability.

• Inflamed Skin: fluid beneath the skin, skin layer is thinner and easier to penetrate

• Corn/Calluses: stratum corneum is thicker, harder to penetrate through the skin layer.

Why do children and premature babies present unique biological factors for TDD?

Children have a larger surface area per unit body weight, and premature babies may be born without a stratum corneum (not fully developed skin layer)

• Medication is able to penetrate and diffuses faster into the skin layer, which can potentially lead to overdose/dose-dumping. Lower doses have to be given within the transdermal patch.

What is the role of humectants in skin hydration, and what are three examples

They are chemicals that draw moisture from deeper skin layers to the surface to increase permeability; examples include glycerol, polyethylene glycol, and hyaluronic acid.

What are the ideal physicochemical properties for a drug to achieve permeation?

Low molecular mass (< 600\,\text{Da}), adequate solubility in both oil and water, a balanced Partition Coefficient (equal parts of oil and aqueous components) , and a low melting point.

What is a major advantage of TTS regarding liver metabolism?

It avoids first-pass liver metabolism, which increases drug concentration.

What are two disadvantages of using Transdermal Therapeutic Systems?

Skin irritation or allergy (usually to adhesive) and higher cost compared to traditional oral medications.

Compare Transdermal and Oral delivery systems regarding first-pass effects and drug levels.

Transdermal delivery reduces first-pass effects and provides constant drug levels, whereas Oral delivery is subject to first-pass effects and may not maintain constant levels.

What are the different advantages that TTS provide?

• Non-invasive

• Convenient and improved patient compliance

• Prolonged effect and controlled release

• Bypasses first-pass metabolism effect to prevent degradation.

What are the biological factors that affect TDD?

• Skin Age

• Skin Condition

• Site of Administration on the body.

What are the physicochemical factors that affect TDD?

Skin Hydration → emollients/humectants → helps to draw in moisture/water-based product into the deeper skin layers
Molecular Weight and Size → small weight → permeates faster and deeper

Ideal molecular properties → Lipinski’s rule of 5 and low melting point (solubility) and balanced partition coefficient.

What are the different components of transdermal patch delivery system?

• Backing Film → protects the contents in the reservoir and patch integrity

• Reservoir → stores the appropriate dose of active drug inside the patch

• Adhesive layer → to help the patch stick properly to the skin for consistent and accurate dosing

• Permeable layer (rate-controlling membrane layer)

How does the active ingredient in the transdermal patch reach its target site/bloodstream?