Drug Delivery: Freeze Drying & Transdermal Treatment

What are the three main layers of the skin?

Epidermis, dermis, and subcutaneous tissue.

Which skin layer is the outermost layer?

Epidermis.

What is the main function of the epidermis?

Provides a waterproof barrier and protects the body.

What structures are found in the dermis?

Connective tissue, hair follicles, and sweat glands.

What is the main composition of the subcutaneous tissue?

Fat and connective tissue.

State two functions of the subcutaneous tissue.

Insulates the body and absorbs shock.

Which layer of the epidermis is the main barrier to drug permeation?

Stratum corneum.

What two substances are present in the intercellular space of the stratum corneum?

Water and lipids.

Why are water and lipids important in the stratum corneum?

They are essential for normal skin function.

What are the two routes of drug permeation through the stratum corneum?

Intercellular and transcellular routes.

What is the intercellular route of drug permeation?

Movement of drug between skin cells.

What is the transcellular route of drug permeation?

Movement of drug through skin cells.

Name the four types of skin preparations.

Liquid, semi-solid, solid, and device.

Give one example of a liquid skin preparation.

Liniment or aerosol spray.

Give one example of a semi-solid skin preparation.

Cream or ointment.

Give one example of a solid skin preparation.

Dusting powder.

Give two examples of skin delivery devices.

Dermal patches and transdermal patches.

Define a transdermal patch.

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

What does TDD stand for?

Transdermal Drug Delivery.

What does TTS stand for?

Transdermal Therapeutic System.

How do transdermal patches deliver drugs?

By passive diffusion through the skin.

Which law explains passive diffusion in transdermal drug delivery?

Fick's First Law of Diffusion.

In transdermal drug delivery, where is the drug concentration highest?

In the patch (donor compartment).

Why do drugs move from the patch into the bloodstream?

They move down the concentration gradient from high to low concentration.

What is one major benefit of maintaining a steady therapeutic drug level?

It improves treatment effectiveness and reduces fluctuations.

List the five components of a transdermal therapeutic system.

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

What is the function of the backing film?

Provides structural support and protects the patch.

What is the function of the drug reservoir?

Stores the drug.

What is the function of the membrane?

Controls the release of drug from the reservoir.

What is the function of the adhesive?

Attaches the patch to the skin.

What is the function of the liner?

Protects the patch before use and is removed before application.

Name one transdermal patch used for pain management.

Fentanyl patch.

Which transdermal patch is used for smoking cessation?

Nicotine patch.

Which transdermal patch is used for ischaemic heart disease?

Glyceryl trinitrate patch.

Which transdermal patch is used for hormone replacement therapy?

Estrogen patch.

Which transdermal patch is used for dementia?

Rivastigmine patch.

Define diffusion.

The movement of molecules from high concentration to low concentration until equilibrium is reached.

State Fick's First Law of Diffusion.

The rate of diffusion is directly proportional to the concentration gradient and surface area and inversely proportional to membrane thickness.

What does D represent in Fick's equation?

Diffusion coefficient.

What does A represent in Fick's equation?

Surface area.

What does Cd represent?

Drug concentration in the donor compartment.

What does Cr represent?

Drug concentration in the recipient compartment.

What does X represent?

Membrane thickness.

What happens to diffusion rate when the diffusion coefficient increases?

It increases.

What happens to diffusion rate when surface area increases?

It increases.

What happens to diffusion rate when concentration difference increases?

It increases.

What happens to diffusion rate when membrane thickness increases?

It decreases.

What is the diffusion coefficient?

A measure of how quickly drug particles move through a membrane.

State two formulation methods that increase the diffusion coefficient.

Use permeation enhancers (e.g. propylene glycol) and physical methods such as microneedles.

How can increasing patch size affect drug diffusion?

It increases surface area and increases diffusion.

How can increasing drug concentration affect drug permeation?

It increases the concentration gradient and increases diffusion.

Why is controlled drug release useful in transdermal patches?

It keeps the drug in a saturated state and maintains the concentration gradient.

How can membrane thickness be reduced practically?

Apply patches to areas with thinner skin.

Name three body sites with relatively thinner skin suitable for transdermal patches.

Upper chest, lower abdomen, and inner arm.

How does inflamed skin affect drug permeability?

It increases permeability.

How do corns or calluses affect drug permeability?

They decrease permeability.

Why may children absorb transdermal drugs more easily?

They have a larger surface area relative to body weight.

Why are premature babies at greater risk of increased transdermal absorption?

They may lack a fully developed stratum corneum.

Why does drug permeability differ between body regions?

Different regions have different stratum corneum thickness and skin appendage density.

How does skin hydration affect transdermal drug delivery?

Increased hydration softens the skin and increases permeability.

What are humectants?

Substances that draw moisture to the skin surface.

Name three examples of humectants.

Glycerol, polyethylene glycol, and hyaluronic acid.

How does molecular size affect skin permeation?

Smaller molecules permeate faster.

What is the ideal molecular weight for transdermal drugs?

Less than 600 Da.

Why should a transdermal drug have balanced oil and water solubility?

It allows movement through both lipid and aqueous layers of the skin.

Why is a low melting point preferred for transdermal drugs?

It improves solubility.

List four advantages of transdermal drug delivery.

Non-invasive, improved compliance, controlled release, and avoids first-pass liver metabolism.

Why is transdermal drug delivery considered non-invasive?

It delivers drugs without injections and is painless.

How does transdermal delivery improve patient compliance?

It reduces dosing frequency and tablet burden.

How does controlled release improve therapeutic outcomes?

It maintains stable drug levels and reduces side effects.

Why does avoiding first-pass metabolism increase drug availability?

The drug bypasses metabolism in the liver before reaching systemic circulation.

List two disadvantages of transdermal drug delivery.

Skin irritation/allergy and higher cost.

What commonly causes skin irritation from transdermal patches?

The adhesive.

How can skin irritation from patches be reduced?

Rotate application sites and avoid leaving patches on one site for too long.

Compared with oral administration, what is one advantage of transdermal delivery?

It avoids first-pass metabolism.

Compared with intravenous administration, what is one advantage of transdermal delivery?

It allows self-administration and unrestricted activity.

A patient wants painless drug delivery with fewer doses. Which dosage form is most suitable?

A transdermal patch.

Why is the upper chest generally preferred over the sole of the foot for transdermal patches?

The skin is thinner, allowing better drug permeation.

A patch is doubled in size while all other factors remain constant. What happens to diffusion rate?

It increases because surface area increases.

A drug has a molecular weight of 900 Da. Is it likely to be suitable for transdermal delivery?

No, because ideal transdermal drugs are usually below 600 Da.

Why might applying a patch to inflamed skin be undesirable?

It may cause excessive drug absorption.

What is freeze drying?

A drying process used for extremely heat-sensitive materials.

Why is freeze drying used for heat-sensitive products?

It removes water without exposing the product to high temperatures during the main drying stage.

List the five stages of freeze drying.

Freezing, primary drying, secondary drying, and packaging (with vacuum sublimation occurring during primary drying).

What phase change occurs during freezing?

Liquid to solid.

What phase change occurs during sublimation?

Solid directly to gas.

Why can't water normally sublime under atmospheric pressure?

Atmospheric pressure is too high (about 101 kPa).

What does a phase diagram show?

The phases of water at different temperatures and pressures.

Name the three phases of water.

Solid, liquid, and gas.

What is a phase boundary?

A line where two phases can coexist in equilibrium.

What is the critical point?

The point where liquid and gas become indistinguishable.

What is the triple point?

The point where solid, liquid, and gas coexist in equilibrium.

Why is the triple point important in freeze drying?

Pressure must be reduced below the triple point to allow sublimation.

What happens to the boiling point of water when external pressure decreases?

It decreases.

What happens to the melting point of ice when pressure decreases?

It increases slightly.

What happens to vapour pressure when temperature decreases?

It decreases.

What happens during shell freezing?

The liquid freezes in a thin shell around the inside of the container.

When is shell freezing commonly used?

For larger volumes.

What happens during centrifugal evaporative freezing?

The solution is spun while vacuum rapidly lowers pressure, causing snap freezing.

Why is centrifugal evaporative freezing used for small volumes?

To prevent foaming after vacuum application.