Transdermal Drug Delivery (3/30/26) - Pharmaceutics II

What types of formulations are used for Dermatological purposes?

Solutions

Suspensions

Gels

Emulsions

Lotions

Creams

What are Lotions, in regards to use for Dermatological purposes?

Either suspensions or emulsions; fluid liquids typically used for their lubricating effect

What are Creams, in regards to use for Dermatological purposes?

Emulsions; typically thick, opaque liquids or soft solids used for their emollient properties that tend to "vanish" or disappear with rubbing

What type of delivery is involved with Transdermal Drug Delivery Systems (TDDS)?

Passage of drug substances THROUGH the skin and into the general circulation for SYSTEMIC effects

What does Percutaneous mean?

How can we measure evidence of Percutaneous drug absorption?

Percutaneous = through the skin

Can measure evidence of Percutaneous drug absorption through:

- Measuring Blood Levels of the Drug

- Detectable Excretion of the Drug or its Metabolites in the Urine

- Clinical Response of a Patient to the Therapy

What are the typical dosage forms used for TDDS?

Gels

Creams

Patches

Ointments

What are Transdermal Drug Delivery Systems (TDDS)?

Advanced, adhesive dermatological preparations designed to deliver a specific, controlled dose of medication through the skin into the Systemic circulation

What are the four main components involved in the formulation of a Transdermal Patch?

1. Backing

2. Membrane

3. Adhesive

4. Liner

What is the main function of the Backing component in Transdermal Patch formulations?

What is it typically made of?

Protects the patch from the outer environment and is impermeable to the transdermal patch components

Provides flexibility

Made of (i) Polyester, (ii) Polyethylene, and (iii) Polyurethane

What is the main function of the Membrane component in Transdermal Patch formulations?

What is it typically made of?

How thick is it typically?

Controls the release of the drug

Made of Natural or Synthetic Polymer

Typically about 2-7 mm thick

What is the main function of the Adhesive component in Transdermal Patch formulations?

What is it typically made of?

What special part of this component is included to promote Skin Permeability? How does it do this?

Binds the patch to the skin

Made of (i) Silicone and (ii) Polyvinyl Acetate, depending on skin adhesion properties

Can include Permeation Enhancers (solvents, surfactants, or misc. chemicals) to promote Skin Permeability by ALTERING ITS STRUCTURE

What is the main function of the Liner component in Transdermal Patch formulations?

Protects the patch during storage and is peeled off before use

How are the components of a Single-Layer Drug-In-Adhesive Transdermal Patch organized, from top to bottom?

TOP

Backing

Adhesive (with Drug mixed in)

Liner

BOTTOM

* NO Membrane layer included

How are the components of a Multi-Layer Drug-In-Adhesive Transdermal Patch organized, from top to bottom?

TOP

Backing

Adhesive (with Drug mixed in)

Membrane

Adhesive (with Drug mixed in)

Liner

BOTTOM

How are the components of a Drug Reservoir-In-Adhesive Transdermal Patch organized, from top to bottom?

TOP

Backing

Small Drug Layer

Membrane

Adhesive

Liner

BOTTOM

How are the components of a Drug Matrix-In-Adhesive Transdermal Patch organized, from top to bottom?

TOP

Backing

Adhesive (with Small Drug Layer)

Liner

BOTTOM

* NO Membrane layer included

What are the four different types of Transdermal Patches according to their component incorporations?

1. Single-Layer Drug-In-Adhesive

2. Multi-Layer Drug-In-Adhesive

3. Drug Reservoir-In-Adhesive

4. Drug Matrix-In-Adhesive

What are some advantages to TDDS?

Non-Invasive

Great Patient Compliance

- Easy to apply and remove

Provide Extended Therapy

- So long as patch is not removed

Drug Therapy can be Terminated Rapidly by Removal of the Patch

Avoid the Hostile GI Environment

- pH, Enzymes

Bypass First-Pass Metabolism

What are some disadvantages to TDDS?

Permeation of Drugs through the Skin is Limited

Stratum Corneum is the Rate-Limiting Barrier

Allergic Contact Dermatitis at the Site of Application

Skin Irritation caused by TDDS

- API, Excipients, Adhesives, and Enhancers

What types of drugs that can commonly cause issues with dangerous dosing are suitable candidates for TDDS?

Relatively Potent Drugs

Where do Dermatological Formulations produce a Local Effect?

ON or IN the skin

What other purposes do Dermatological Formulations serve, besides specific therapeutic actions of included APIs?

Serve as:

- Protectants

- Lubricants

- Emollients

Give a list of example treatment options that can be fulfilled by Dermatological Formulations.

Minor Skin Infections

Itching

Burns

Diaper Rash

Insect Stings and Bites

Athlete's Foot, Corns, Calluses

Dandruff

Acne, Psoriasis, Eczema

Compared to traditional topical creams, what type of effect do Transdermal Drug Delivery Routes offer?

Transdermal - SYSTEMIC Effects

Topical - LOCAL Effects

What three processes result in Percutaneous Absorption?

1. Potential of the Drug to cross the Stratum Corneum

2. Potential of the Drug to leave the formulation

3. Influence of the formulation on the Stratum Corneum

What four generalizations can be made about the Percutaneous Absorption process?

1. LARGER SURFACE AREA of Application = More Drug is Absorbed

2. HYDRATING Formulations / Dressings generally ENHANCE percutaneous absorption

3. Greater the amount of FORMULATION RUBBING, the greater the absorption

4. LONGER CONTACT of formulation with skin = greater the absorption

^ SA = ^ Absorption

^ Hydration = ^ Absorption

^ Rubbing = ^ Absorption

^ Contact = ^ Absorption

What is the largest and heaviest organ of the body?

What percent of the total body weight does it comprise?

The Skin

Comprises 17% of the total body weight

What is the total surface area of the Skin?

Thickness?

Total SA = 1.2 - 2.2 m2

Thickness is 3 - 5 mm

What is the Outermost layer of the Skin?

Middle layer?

Innermost layer?

Outermost Layer = EPIdermis

Middle Layer = Dermis

Innermost Layer = HYPOdermis

What are the three main functions of the Skin?

1. Regulates Body Temperature

2. Regulates Body Fluids

3. Protective Functions (microbial, chemical, radiation, thermal, and electrical barriers)

Which layer of the skin is the major barrier to Transdermal drug absorption?

How many sublayers is it comprised of?

Which of these sublayers is the PRIMARY barrier?

Epidermis Layer is the major barrier

Comprised of 5 sublayers

Primary barrier to drug absorption is the STRATUM CORNEUM (SC) Layer

What is the Rate-Limiting Step to Transdermal Drug Absorption?

Penetration through the Epidermis Layer (subsequently, the Stratum Corneum)

What type of structure does the Stratum Corneum have?

"Brick Wall" structure

What is the Dermis Layer of the Skin comprised of?

What is it the main site for?

How thick is it?

Comprised of an extensive Lymphatic Network and four main components

- Collagen, Elastin, Reticulin, Ground Substance

Main site for transdermal absorbed drugs to enter the systemic circulation

2-3 mm thick

What are the four components of the Dermis Layer?

What percent of the layer do each of them comprise?

Collagen - 75%

Elastin - 4%

Reticulin - 0.4%

Ground Substance - 20%

What is the Hypodermis Layer of the Skin comprised of?

What is it the major site for?

What are its main functions?

Give another name for this layer.

Comprised of loose connective tissue and fat

Major site for Fat Storage (~50% of body fat)

Main functions:

- Provide mechanical cushion and a thermal barrier

- Serves as contact layer between Skin and underlying body tissues (ex. Muscles and Bone)

Also called the SUBCUTANEOUS Layer

What are the three main mechanisms for Transdermal Drug Absorption?

Which two do not contribute as much to Percutaneous drug absorption?

1. Across the Intact Stratum Corneum Layer

2. Through the HAIR FOLLICLES with the Associated Sebaceous Glands

3. Through the SWEAT GLANDS

Mechanisms 2 and 3 do not contribute as much due to a fractional amount of area being available for these two routes (~0.1%)

What is Percutaneous Absorption the direct result of?

Direct result of penetration of the drug through the Hypodermis / Subcutaneous Layer

What is the SC Layer comprised of?

40% Protein (mainly Keratin)

40% Water

Balance of Lipids (Triglycerides, Free FA's, Cholesterol, and Phospholipids)

When does a drug become available for absorption into the Systemic Circulation?

Only after the drug reaches the Vascularized Dermal Layer

What type of process is Transdermal Absorption?

What law dictates this process?

Passive-Diffusion Process

Dictated by Fick's First Law of Diffusion

What is Fick's First Law of Diffusion?

dM / dt = AP∆C

where,

dM / dt - total flux transported through a unit area of skin PER unit time in steady state (microgram / hr)

A - area of skin

P - permeability coefficient

∆C - drug conc. gradient across the skin

What two things can be changed to enhance permeability percutaneously?

Altering the structure of the skin, OR

Increasing the solubility of the drug in the skin

What three factors are responsible for affecting Transdermal Absorption?

1. Physical and Chemical Properties of the Drug

- MW (<400 Da preferred)

- Solubility (in both Lipids and Water essential)

- Partitioning Coefficient

2. Formulation

- Liposomes can improve absorption

3. Exposure Time

- Longer the TDDS is permitted to remain in contact with the skin, the greater the drug absorption

What two types of techniques can be used to enhance Transdermal Absorption?

1. Chemical Enhancement Techniques (via Penetration Enhancers)

2. Physical Enhancement Techniques

What changes occur as a result of using Chemical Enhancement Techniques to enhance Transdermal Absorption?

Give examples of these types of techniques.

Alteration to the structure of the lipids in the skin, causing a decrease in their diffusion resistance

Enhancement of the drug solubility within the skin

Examples:

- Dimethyl Sulfoxide (DMSO)

- Azone

How does DMSO enhance Transdermal Absorption?

Azone?

Dimethyl Sulfoxide (DMSO) - extracts lipids and makes the Stratum Corneum more permeable

Azone - partitions into bilayer lipid to disrupt the packing arrangement and, thereby, increasing the fluidity of the lipid bilayer

How does hydration affect Penetration Enhancers?

How can we increase the hydration of the skin?

Hydration can open the compact structure of the Corneum Stratum, causing it to SWELL 3x its original thickness and ABSORB 5x its weight in water

Can increase the hydration of the skin by preventing water loss (TDDS can act as occlusive moisture barriers)

What are the five types of Physical Techniques we use to increase Transdermal drug absorption?

1. Skin Abrasion (Microdermabrasion)

2. Electroporation

3. Iontophoresis

4. Sonophoresis

5. Microneedles

What is Microdermabrasion?

Physical technique in which the Stratum Corneum is partially removed via light abrasion to increase Transdermal absorption

What is Electroporation?

Physical technique in which SHORT PULSES OF HIGH VOLTAGE CURRENT are applied to create transit small pores in the phospholipid bilayer of the Stratum Corneum, in an effort to increase Transdermal absorption

What is Iontophoresis?

Physical technique in which drug movement through the skin is facilitated by APPLIED ELECTRICAL CURRENTS in an effort to increase Transdermal absorption

Charged drugs are moved via Electrophoresis

What was the first commercially approved Iontophoretic patch system?

LidoSite, which was used to deliver Lidocaine for fast, dermal anesthesia

What is Sonophoresis?

Physical technique in which use of ULTRASOUND ENERGY is used to enhance Transdermal drug delivery and absorption

Ultrasound disrupts the Stratum Corneum lipid structure, causing an increase in skin permeability

What is the Microneedle Technique?

Physical technique in which microneedles are used to penetrate the Stratum Corneum and Epidermis WITHOUT reaching nerve endings present in the Upper Dermis, in an effort to increase Transdermal absorption

Painless injection is used and made up of Silicone / Polymer

Which physical technique used ultrasound energy to enhance transdermal drug delivery?

Sonophoresis

Which physical technique penetrates the skin without reaching nerve endings of the upper dermis to enhance transdermal drug delivery?

Microneedles

Which physical technique facilitates the movement of drugs through the skin via an applied electrical current to enhance transdermal drug delivery?

Iontophoresis

Which physical technique uses short pulses of voltage current to create transit small pores to enhance transdermal drug delivery?

Electroporation

What are MicroHyala?

Dissolving microneedles made from pure Hyaluronate and pure Collagen, that dissolve in the skin within 60-90 minutes and effectively release the API for max penetration

What is a Macroflux Patch (Alza)?

Patch used for transdermal delivery of Proteins, small molecule drugs, and Vaccines

What are Microneedle Skin Roller Dermatology Therapy Systems used for?

Improving elasticity of the skin and to make you look younder without painful treatment

What is RF-MicroChannel Technology?

Which layer of the skin does it affect?

How long does it take to do what it does?

What is it used to treat?

High frequency alternating current is transferred through these microelectrodes, causing localized ablation of the skin

Penetrates only the OUTER layer of the skin (no pain, no blood)

MicroChannels are generated within Milliseconds and stay open for more than 24 hours

Used to treat Osteoporosis