Transdermal Drug Delivery Systems- Miroshynk

What are the 3 main transport routes of drugs in transdermal systems?

1. intracellular/transcellular

2. intercellular

3. shunt routes

   • sweat pores/ hair follicles

What physiological factors affect permeation (movement of the drug)?

• body site

• race

• age

• skin condition

• skin hydration

“BRASS”

What physiochemical factors affect permeation (movement of the drug)?

• MW

• Effective dose of a drug

• Partition coefficient (log P)

What formulation factors affect permeation (movement of the drug)?

• drug conc

• pH of vehicle

• surface area

• larger the TTDS= more drug absorbed

• exposure time

What are the advantages of TDDs?

• bypass 1st pass metabolism

• continuous/controlled drug delivery

• avoid GIT

• self-administrable

• noninvasive/painless

• inexpensive

• possible transdermal VACCINE delivery (could improve immune response)

What is a transdermal patch?

dosage form designed to deliver a constant and controlled therapeutic dosage across the skin over extended periods of time for SYSTEMIC therapy

(key words: skin and systemic)

What are the 3 types of transdermal patches?

1. drug-in-adhesive (DIA)

2. drug-in-matrix (DIM)

3. reservoir system

(hint: as you go from 1-3 the patches get more complex. I think of DIA as the simplest, and reservoirs as most complex)

Describe the “anatomy” or each part of a transdermal patch:

• protective liner

• adhesive

• backing layer

• drug matrix

• drug reservoir

• membrane

• protective liner- temporary covers adhesive, removed before application

• adhesive- part that maintains contact w/ the skin, should be non-irriating/allergic, and compatible, serves as matrix for DIA

• backing layer- film, protects the patch from the outside world

• drug matrix- ONLY in DIM, a blend of drug+polymer

• drug reservoir- ONLY in RESERVOIR systems, isolated drug donor layer, contains a liquid or gel blend of the drug+polymer, viscosity is important

• membrane- semipermeable, optional, usually used to separate reservoir and adhesive

For Drug-in-adhesive and drug-in-matrix transdermal patches the drug matrix is a blend of drug+polymer. What polymers are used?

• cellulose derivatives

• PVP

• POVIAC

For each type of transdermal patch, what layer or “part” of the patch contains the drug for administration? (hint: look at the name)

• Drug-in-adhesive

• Drug-in-matrix

• Reservoir

• Drug-in-adhesive: ADHESIVE LAYER

• Drug-in-matrix: DRUG MATRIX LAYER

• Reservoir: RESERVOIR LAYER

True or False: A drug-in-adhesive transdermal patch contains a reservoir.

false

Which of the transdermal patches are considered to have matrix systems and which have membrane controlled systems?

matrix systems- Drug-in-adhesive and drug-in-matrix

• even tho DIAs don’t have matrix in the name the “adhesive” layer is considered the matrix layer

membrane controlled release- reservoir systems

What are the disadvantages of matrix systems (DIAs and DIMs)?

low drug loading

What are the disadvantages of membrane controlled systems (reservoir patches)?

• only potent drugs can be used

• only small, unionized, moderately lipophilic drugs can be used

• possibility of site reactions (dermitits)

• patches contain lots of residual drugs

What are the advantages of membrane controlled systems (reservoir systems)?

• higher drug loading

• as long as reservoir full = release rate is constant

Drug Matrix systems can either be infinite or finite dose formulations. What do each of these mean?

Finite- withOUT excess of drug, no drug reserve

Infinite- WITH excess of drug, drug reserve

Is this permeation profile, infinite or finite?

finite

Is this permeation profile, infinite or finite?

infinite

Permeation (movement of the drug) can be enhanced in what 2 ways?

physical OR chemical

How does chemical permeation enhancement work?

increases skin permeability by REVERSIBLY damaging or altering the physicochemical nature of the stratum corneum(skin) to reduce its diffusion resistance

• basically: altering the skin so the drug can better absorb

How does physical permeation enhancement work?

enhancing skin penetration through physical means like electroporation, iontophoresis, sonophoresis, and microneedles

What is the MOA of chemical permeation enhancers?

• increase skin hydration

• expand intracellular lipids and lipoprotein channels

What is the MOA of electroporation? (a physical permeation enhancer)

creates aqueous pores in lipid bilayers by applying short electrical pulses

What is the MOA of Iontophoresis? (a physical permeation enhancer)

passage of a constant electrical current onto the skin through

• electromigration

• electroosmosis

• passive diffusion

What is the MOA of Sonophoresis? (a physical permeation enhancer)

uses low/high frequency ultrasound to produce cavitation, microstreaming, and heating

What is the MOA of Microneedles? (a physical permeation enhancer)

minimally invasive devices that disrupt the stratum corneum by creating microchannels

Examples of chemical permeation enchancers:

• water

• alcohols

• DMSO

• fatty acids

• surfactants

What is the goal of in vitro release testing and how is it measured?

goal: determine route and amount of drug permeated through skin

measured using DIFFUSION CELLS (Ex: Franx)

PRACTICE

What is the most significant barrier to transdermal drug delivery?

a. molecular size of drugs

b. skin structure

c. patient noncompliance

d. a high cost of TDDS

b

PRACTICE

A patient asks a pharmacist whether or not she can cut her transdermal scopolamine patch in halves and use a half patch for her daughter. What should you, as an attending pharmacist, respond to this patient?

no-you cannot cut it in half

PRACTICE

The passage of a constant electrical current onto the skin is known as ______________________.

a. electroporation

b. iontophoresis

c. sonophoresis

d. microneedles

b

PRACTICE

Which of the following can be used as the chemical permeation enhancers?

• Water

• Fatty acids

• Ethanol

• DMSO

• Glucose

• Surfactants

water, fatty acids, ethanol, DMSO, surfactants