Transdermal Drug Delivery Systems

What is a topical dermatologic product?

It is designed to deliver a drug to the skin in treating dermal disorders

What is the topical dermatologic product’s target organ?

Skin

What is a transdermal preparation?

It is designed to delivery drugs through the skin to the general circulation for systemic effect

Is the skin the target site of transdermal preparations?

No

What are the advantages of transdermal drug delivery systems?

• Avoiding GI absorbing variability because of pH difference, enzymes, food & possible interaction with other drugs

• Can deal with unconscious patients or those who are vomiting or have diarrhea

• Avoiding first-pass metabolism

• Improving patient compliance due to low dosage frequency

• Immediate termination of treatment is possible

• Rapid identification of medicine in emergencies

What are the disadvantages of transdermal drug delivery systems?

• Only potent drugs are suitable because of limited permeability

• Not suitable for sensitive skin

• Not for drugs/excipients that cause irritation or sensitization &/or diseases skin

• Manufacturing technical issues

What are the factors affecting percutaneous absorption?

• Physiochemical properties of drugs

Both aqueous and lipid solubility to some extent is needed

• Skin properties

• Presence of additives

What is better to be transported across the skin?

Unionized form

What type of drugs prefer transcellular route?

Nonpolar/lipophillic drugs

What type of drugs favor the intracellular route?

Polar drugs

What kind of drug cannot pass through the membrane?

High molecular weight

What type of skin has greater absorption?

Abraded skin or skin with less stratum corneum

What parts of the body show less absorption?

Palm and sole

What areas of the body show better absorption and why is that the case?

Regions behind the ears and on the chest because of a high blood supply

What increases absorption and why?

Occlusion because it keeps the skin hydrated and increases the temperature

How much does steroid permeation can be increased by occluding the skin?

100-fold

What type of vehicles are more suitable for the skin?

• Easily cover the skin

• Mix with sebum

• Retain the moisture

• Bring the drug in contact with the skin

What is the purpose of surfactants?

Enhancing percutaneous absorption of polar drugs and reducing surface tension

What does surfactants increase?

Solubility and drug dispersion

What are the 3 pathways by which a drug can pass through the skin?

• Intact horny layer

• Hair follicles

• Sweat glands

What does the rate of the drug movement across the stratum corneum depend on?

• Drug concentration in the vehicle

• Aqueous solubility

• Oil-water partition coefficient between stratum corneum and product’s vehicle

True or false: A higher drug concentration and lower body lipophilic concentration always ensure maximum tissue penetration.

False

• Higher concentration does speed up diffusion by creating a steeper gradient

• Lower/moderate lipophilicity stops the drug from getting trapped in fatty tissues

What is the most limiting or the most outermost skin layer?

Stratum corneum

What are the two types of transdermal patches?

• Monolithic (matrix) system

• Membrane-controlled (reservoir) system

What controls the drug release in a reservoir system?

Control membrane

What are the features of the monolithic system?

• Drug matrix layer (solid form) in between backing and frontal layers

• Drug is uniformly mixed with polymer(s) that control drug release

What controls the rate at which the drug is released for percutaneous absoprtion?

Polymer matrix

What are some examples of the monolithic system?

• Nitro-Dur

• Vivelle

What are the features of a membrane-controlled (reservoir) system?

• Drug reservoir remains as liquid or gel

• Gives more uniform release than monolithic systems

What controls the drug release in a reservoir system?

Polymeric membrane

How does it initiate prompt drug absorption?

A small amount of the drug is frequently placed in the adhesive layer

What are some examples of reservoir systems?

• Transderm-Nitro

• Transderm Scop

What is the purpose of the backing layer?

• Prevents drug loss from system

• Protects system from environmental entry

How is the backing layer functioning?

• It is occlusive

• It prevents moisture loss from the skin to hydrate the site of application

• Enabling increased drug penetration

What are some examples of backing layers?

• Transparent or pigmented films of polyester, polypropylene, polyethylene, and polyolefin (aluminized or not)

What makes up a control membrane?

Ethylene-vinyl acetate with micro-porous structures of varying pore size

• Polyethylene

• Polypropylene

What makes up the matrix polymer?

Ethylene-vinyl acetate + methacrylic acid

What is the purpose of the adhesive layer?

Maintaining contact with the skin

What are the features of adhesive layer?

• Peripheral adhesive: In a wide strip around the outer edge of TDDS

• Face adhesive: Covers entire face of TDDS, non-irritating

What is used for an adhesive layer?

• Silicone

• Polybutyl acrylate

• Polyisobutylene

What can help penetrate through the stratum corneum?

• Chemical enhancers

• Physical methods

What are the chemical enhancers?

Increasing transdermal absorption by reversibly damaging or altering the physicochemical nature of stratum corneum

Ex: Dimtheylformamide, oleic acid PEG

What are the physical methods?

Used to increase skin permeability

What does alcohol, alkyl methyl sulfoxides, and polyols do?

• Increase solubility

• Improve partitioning coefficient

What do DMSO and ethanol do?

• May extract lipids → Stratum corneum more permeable

What is iontophoresis?

Application of low-intensity electric current to facilitate permeation of charged drug into skin

What if there is no charge?

You cannot use the method

How does iontophoresis work?

• A drug reservoir is placed on the skin under the active electrode with the same charge as the drug

• Counter electrode is positioned elsewhere on the body

Does the active electrode effectively attract or repel the active substance and forces it into the skin?

Repel

What is an example of iontophoresis?

Lidosite topical system delivers lidocaine and epinephrine

What is electrophoresis?

Large voltage for a short period of 10 us to 100 ms, producing hydrophilic pores (aqueous pathways) across the skin barrier

What do the pores allow?

Passage of macromolecules via a combination of diffusion, electrophoresis, and electro-osmosis

What is sonophoresis?

High-frequency ultrasound is used to enhance percutaneous absorption

What does ultrasound do to the skin?

• Increase temperature

• Increase intracellular space

• Deformation of lipids

What does sonophooresis result in?

Increase in fluidity of stratum corneum lipid + increase of diffusivity of molecules through the skin barrier

What are microneedles used for?

Placed onto skin surface so they can penetrate the stratum corneum and epidermis without reaching the nerve endings present in upper dermis

What is the structure of microneedles?

Solid or hollow or filled with drugs and connected to a reservoir

How can skin permeation be tested?

• In-vitro using Fick’s laws of diffusion

• Performed in specialized equipment called diffusion cells or chambers

• Each cell has donor and receiver compartment separated by membrane

What are some patient counseling words?

• Never cut a TDDS to have a reduced dose; system’s integrity would be lost

• Avoid skin lotion, it will affect skin hydration and drug release

• Press the patch firmly against the skin

• TDDS should not be rubbed by clothing

• Do not remove patch while showering, bathing, and swimming

• Should always wear TDDS for the full period stated in the product information sheet or by physician

• Should clean hands thoroughly before applying TDDS

• Should apply only at sites that are recommended by their manufacturer

• Contact their physician in case of irritation, intolerance, rash, etc.