Exam 2: Transdermal

Movement of compounds/drugs across the skin into systemic circulation

Transdermal Delivery

Outer, epithelial portion of the skin

Epidermis

Dead cells of the epidermis and poses major resistance to transdermal transport

Stratum Corneum

T/F: Transdermal Drug Delivery (TDD) avoids first pass metabolism in the liver

True

What type of transdermal patches can be predictably controlled over a long period of time

Simple Matrix

Pathways of skin drug transportation

Transcellular

Intercellular

Appendageal

What transportation pathway has the drug remain in the lipid domain via tortuous pathway through the skin

Intercellular

What transportation pathway is the main route to cross the Stratum Corneum (SC)

Intercellular

What transportation pathway involves continuous partitioning of the drug between cornified cells, extracellular lipid bilayers, viable epidermis, and the papillary layers of the dermis

Transcellular

What transportation pathway is a rate limiting step for drug absorption for the skin

Intercellular

What transportation pathway that crosses the skin via Shunt pathway (hair follicle, sweat gland)

Appendageal

The shunt pathway is about __ % of the total skin

0.1

What type of additives are used to increase Transdermal Drug Delivery (TDD)?

Penetration Enhancers or Accelerants

Physical approaches to enhance Transdermal Drug Delivery (TDD)

Iontophoresis

Electroporation / Electropermeabilisation

Phonophoresis

Microneedle

Thermal methods

Examples of enhancers that impact drug diffusion across the Stratum Corneum (SC)

Alcohols

Surfactants

Fatty Acids

Phospholipids

Sulfoxides

Examples of enhancers that alter drug partitioning into the Stratum Corneum (SC)

Propylene Glycol

N-Methyl Pyrollidone

What molecular aspects of diffusion enhancers to increase permeability?

Long Alkyl Chains

Polar Head Groups

What interacts with long chains of the intercellular lipids in diffusion enhancers?

Long Alkyl Chains

What interacts with polar portions of lipids to increase permeability?

Polar Head Groups

Partitioning enhancers shift the ___ of the Stratum Corneum (SC) towards the enhancer

Solubility

Term used to “carry out”

Phoresis

Ionic drug forms that can be carried out with a small current and driven into the body through the skin

Iontophoresis

T/F: Electric currents decrease skin permeability

False

The application of high voltage pulses which leads to transient structural perturbation of lipid bilayer

Electroporation

Use of ultrasound energy to enhance permeation by creating cavities in the skin

Phonophoresis / Sonophoresis

Method used to locally heat and ablate (remove) holes in the Stratum Corneum which increases skin permeability

Thermal

Uses for Thermal Methods

Deliver conventional drugs

DNA vaccines to animals

Extract interstitial fluid glucose from humans

Factors for selecting Transdermal Drug Delivery

Drug potency

Toxicity

Oil-Water Partition Co-efficient (log P)

Polarity and Charge

Categories for Transdermal Patches

Monolithic Systems

Membrane Controlled Systems

Uniformly disperse and diffuse drugs in a non-biodegradable polymer

Monolithic Systems

Release rates of Monolithic Devices ___ as a function of time and distance (non-steady state)

Decrease

T/F: Micro-Needles can be solid or hollow connected to a reservoir that contains the drug

True

T/F: Micro-Needles can reach nerve endings and can cause pain

False

In a membrane controlled system, the reservoir (core) is surrounded by what type of membrane

Polymer

A membrane controlled system has a ____ (ready-state) membrane that has constant thickness, diffusivity, and solubility coefficient for a drug

Rate-Controlling

Disadvantages of TDD

Only relative potent drugs are suitable

Can irritate skin and necessitate discontinuation