Trandermal Drug Delivery

Define transdermal drug delivery and explain why it is used for systemic rather than just localized activity.

Describe the therapeutic goals of a TD patch and compare this profile to oral dosing

Explain why transdermal systems avoid first-pass metabolism and why this matters clinically.

What are some disadvantages to trandermal drug delivery?

What does MEC and MTD?

What are the two types of systems for TS delivery ?

1) Passive systems

2) Active systems W

What are passive systems?

rely on diffusion and no active energy input

• SC (stranum corneum) is the rate-limiting step

What explains diffusion rate for passive systems?

Fick’s law

J = DKC/L

D = diffusion coefficient

K - partition coefficient (where the drug wants to go in delivery system or skin)

C = concetration gradient

L = length/distance it has to travel through RLS

Draw the SC

• keratin blocks

• covered by lipid mortum

• D (drug diffusion through layer)

• skin surface

What are two types of passive patches ?

1) Reservoir patch

2) Matrix patch

Draw reservoir patch

1) drug in solvent

2)RLS (SC)

3) Poly vinyl acetate adhesive

Draw matrix patch

1) drug embedded in silicone matrix

2) adhesive

How can you enhance skin penetration? What can you manipulate?

1) Skin:

• Water: hydrate SC so hydrate keratin causing them to swell and loosen up the packed structure thus creating more space for drugs to diffuse (increases D)

• increase K for HPL drugs

• Lipids: insert themselves into layers thus disrupting the packing and increase J

2) Formulation

• ethanol: increase C

• surfactants:Insert into SC→ loosen structure → increase permeability

• DMSO

Why is the stratum corneum the rate-limiting step for passive diffusion?

It’s dense, keratinized, dehydrated and lipid rich thus low permeability

What does “sink conditions” mean in the context of dermal drug delivery?

Once the drug gets through the skin the body immediately removes it (through bloodstream) thus keeps the gradient big (continuous steady diffusion)

What determines whether a drug localizes in the aqueous vs lipid portions of the patch?

Depends on hydrophobicity and lipophilicity which determines K (SC is HPB and dry)

What is an active system?

requires energy to increase flux

What is iontophoresis?

Uses a low electric current to push charged drugs across the skin

• load drugs onto the positive side

What are the physical principles behind iontophoresis?

1) electroosmosis: movement of water induced by ions → drags drug molecules with it

2) electromigration: electrode repels charged drug molecules → drive them into skin

3) passive diffusion

What formulation considerations affect iontophoresis (ionic strength, pH)?

1) Ionic strength of solution(high → shield drug → lower flux)

2) pH (if acid ionized = negatively charged and if base ionized = positively charged)

Why must the drug be ionized for iontophoresis to work effectively?

so they can respond to the electric field

How does pH relative to pKa determine ionization and therefore delivery efficiency?

Drug must be ionized

What “two handles” can be changed to alter flux in iontophoresis, and what are their effects?

1) [Drug]

2) Amp

Why does increasing drug concentration eventually saturate the transport rate?

Increase [D] = increases flux

• until system gets saturated which then drug doesn’t increase flux In

Why does increasing applied current amplitude plateau in terms of flux?

Increase Amp = Increase flux until system is saturated

What is sonophoresis and what frequencies are typically used?

Use of ultrasound to enhance permeation

What are the three mechanisms by which ultrasound increases skin permeability?

1) Cavitation: forms microbubbles which collapse and disrupt SC → creating pores

2) thermal expansion: loosens structure

3) convective flow: holes through skin

How do ballistic “gene gun” particles work and why are they coated with gold?

gold particles coated with DNA or drug and fired into skin at high velocity, use gold b/c easy to coat and biocompatible

What kinds of microneedles did he present in class?

1) Biodegradable needles

2) Absorbed (vaccines)

3) orginical: solid silicone needs

What are microneedles?

Puncture SC without reaching nerces allowing drug to bypass SC