Topically applied devices that deliver drug across the skin for systemic effects at a pre-determined and constant/consistent rate

The rate of drug delivery may be controlled either by the patch or by the skin depending on the type of patch used 

The rate of drug delivery is smaller than the absorption capacity of the skin, and is the limiting step to the percutaneous absorption of a drug.

Drug delivery from patch depends on the controlling system 

The rate of drug delivery is higher than the absorption capacity of the skin - the skin is a reservoir for the drug

Drug delivery from the patch follows zero-order release kinetics: same amount of drug released/unit time 

First commercially available patch was approved y FDA in 1979: Scopolamine (Transderm Scop)

Best-selling: nicotine patch - releases nicotine over 16 hours

Other drugs:

Estradiol: Climara, OrthoEvra

Nitroglycerin: Nitrodisc

Fentanyl: Duragesic 

NO!

Gel: Hydroalcoholic gels containing a combination of permeation enhancers

Examples: Testosterone, estradiol

Ointments: Nitroglycerin

Spray (under testing): Estradiol 

A relatively large amount of drug would have to be applied

The hands must be washed thoroughly to remove residual potent substances such as testosterone or nitroglycerin

The area of contact is variable 

Increase residence time compared to other topical formulations - increase absorption

Area (cm2) of application does not vary

Skin occlusion - backing film

Easy to terminate therapy

The activity of drugs with small half-life may be extended

Provide extended therapy with a single application

Patient comfort 

Avoids first-pass hepatic metabolism

Avoid gastro-intestinal difficulties

Substitute oral delivery

Non-invasive 

Skin irritation

Few drugs are ideal candidates: MW, solubility (logP),ionization

MW < 500

log P > 3 = very lipophilic --> retention in the SC

log P < 0 = drug very hydrophilic --> does not cross the SC 

Clonidine

Estradiol

Lidocaine

Nicotine

Nitroglycerine

Scopolamine 

Drug should be potent but not have a long half-life

Potency of drug affects design of patch because of absorption capacity of the skin

Don't want a long half-life because the patch provides constant rate of drug delivery for long periods of time. 

Composition relatively invariant in use

System size reasonable

Defined site for application

Application technique highly reproducible

Delivery is efficient 

Pieces of plastic dipped into a drug solution in alcohol; the plastic had adhesive around the edges

They created a significant number of skin reactions, fell off very frequently, and delivery was not consistent. 

Depending on the formulation that contains the drug

Drug-in-adhesive

Matrix controlled device = monolithic patches

Membrane-controlled device = reservoir patches 

The adhesive has two functions: it is the glue that keeps the patch attached to the skin, and it acts as a matrix that holds the drug.

Skin controls the rate of drug permeation 

Estradiol (Climara, Berlex)

To treat symptoms from menopause, female castration, primary ovarian failure, and other disorders related to deficiency of estrogen production

Why transdermal estradiol? Rapid and extensive hepatic metabolism: bypass first-pass effect

Acrylate adhesive matrix containing the drug

Patches applied once or twice/week 

Concentration of the drug within the adhesive direclty affects the "stickiness" of the adhesive

Need for large quantities of drug: increase the size of the patch or reapply patch more frequently 

With or without drug excess.....

Without drug excess:  As drug concentration in the patch decreases, the transport through the skin decreases.

With drug excess:  high drug concentration to ensure saturation of the Stratum Corneum 

Patch for transdermal delivery of testosterone, for treatment of testosterone deficiency

Testoderm (Alza): Matrix Patch

-Testosterone in matrix of ethylene-vinyl acetate copolymer

-Should be applied in the scrotal skin

-Applied daily 

Membrane controls drug delivery

Drug reservoir in liquid or gel form

A small amount of drug can be added to the adhesive layer to initiate prompt absorption and therapeutic effect

As long as the drug reservoir is saturated, the release rate is constant 

Esteraderm (Novartis)

-Estradiol reservoir: hydroxypropyl cellulose and alcohol

Transderm Scop (Novartis)

- Scopolamine reservoir: mineral oil, polyisobutylene

- Scopolamine in the adhesive layer

Peripheral: present only at the edges of the patch

Face: covers the entire face of the patch - must not interfere with drug delivery 

Should not irritate or sensitize the skin

Allow fast adherence with minimum pressure

Remain in place for the intended period of time but must be easy to peel off

Compatible with other components

When used in the face of the patch, should not influence drug release 

- Retains skin moisture and hydrate the site of application, thereby increasing skin penetration

- avoids evaporation of vehicle and changes in drug concentration in the reservoir

- avoids back-diffusion

- Flexibility

- Impermeable: do not allow drug release and protect product during use

- May be transparent or pigmented. Ex: polypropylene or polyethylene 

- Addition of chemical penetration enhancers: in the matrix, reservoir, adhesive layer.

Use of physical strategies:

- Electronically and mechanically mediated delivery: microneedle, iontophoresis, sonophoresis