Transdermal Drug Delivery II

Release liner

temporarily covers the adhesive and the layer that is removed

What are removable release liners made from?

polymers such as poly(ethylene vinyl acetate) or aluminum foil

Release liner requirements

• must easily peel away from adhesive 

• bonded firmly enough to prevent accidental removal

• occlusive to prevent loss of volatile patch components

Transdermal adhesive materials

acrylates, polyisobutylene, or polysiloxane

Adhesive requirements

• stick to skin for patch’s lifetime

• nonirritating and nonallergenic

• compatible with drug and other excipients

• allow patch to be removed painlessly without leaving adhesive residue on skin surface

Rate-limiting membrane

controls the drug release, used to separate reservoirs from underlying adhesive

Membrane materials

polymers such as poly(ethylene-vinyl acetate)

Drug matrix/reservoir

prepared by dissolving the drug and polymers in a common solvent before adding in other excipients such as plasticizers

Plasticizers

additives used in polymers to make them more flexible, less brittle, easier to bend or stretch

Plasticizer examples

glycerin, PEG, triacetin

How can the viscosity of the matrix be modified?

by the amounts of polymers incorporated or by cross-linking polymers in the matrix

Reservoir composition

may use a viscous liquid, such as silicone or a cosolvent system, occasionally with ethanol, into which the drug is dissolved and dispersed

What type of backing layer may be used for relatively short-use small patches and why?

occlusive backing layer

• will hydrate underlying skin, which can increase delivery

Example materials of backing layers

polyethylene or polyester films

What type of backing layer should be used for longer-term use?

permit some vapor transmission (breathable)

Example long-term backing layer material

poly(vinyl chloride) films

Drug-in-adhesive patch

simplest and most common, widely used to deliver nicotine, oestradiol, and nitroglycerine

How are simple drug-in-adhesive patches formed?

• dissolving or dispersing drug within an adhesive

• coated onto a backing layer

• release liner is applied

How do simple drug-in-adhesive patches compare to other systems?

• thinner

• more flexible

• may aid patient comfort and adherence

Drug-in-matrix patch

drug can be included in a separate matrix which can be formulated to increase the drug content in the system or to control drug release

Drug-in-matrix components

• often a polymeric mixture such as polyvinylpyrrolidone and poly(vinyl acetate)

• potentially with the addition of a plasticizer such as glycerol

• hydrogels

How will drug from drug-in-matrix be released?

will partition into and diffuse through the underlying adhesive layer

Rate-limiting membrane-type patch

more complex rate-limiting membrane systems typically contain the drug in a reservoir but with release controlled through a semipermeable membrane

Rate-limiting membrane-type patch reseroir

may be liquid or gel and can be designed to contain high drug loadings

Effect of water as a transdermal absorption enhancer

hydration increases penetration of most active compounds

Chemical penetration enhancers

increases skin permeability by reversible damaging or altering the stratum corneum to reduce diffusional resistance

Can chemical penetration enhancers be used for delivery of macromolecules?

no, they aren’t good enough

Ideal chemical enhancer properties

• no pharmacological effect

• specific

• penetration enhancement effect is reversible

• chemically/physically stable

• compatible with all components of TDDS

• odorless/colorless

• inexpensive

Ethanol as a chemical penetration enhancer

most used, increases permeation of hydrophilic drugs but decreases the permeation of lipophilic drugs

DMSO as a chemical penetration enhancer

most widely used, high concentration is needed for enhancement efficacy