PDD: L11 Transdermal Drug Delivery

Topical (or semi-solid) dosage forms

• Examples: …, …, …

• Target organ: …

• Promote drug … in skin

gels, ointments, emulsions, skin, residence

Transdermal dosage forms:

• Examples: …

• … delivery

• Promote drug migration … the skin to the underlying blood supply without buildup in the skin

patches, systemic, through

Advantages and Disadvantages of Transdermal Drug Delivery Systems (TDDS):

• Avoid GI drug absorption difficulties

  • Poor bioavailable drugs when orally delivered

  • Avoid … effect

  • Patient conditions: vomiting, diarrhea

• … compared to parenteral routes

• Extended therapy with improved patient compliance

  • Short half-life drugs that require frequent dosing

• Therapy may be terminated … by removal of the patches

• Can be easily and rapidly …

• Only … drugs are candidates because percutaneous absorption is not efficient

• Patients may develop contact …

first-pass, Noninvasive, rapidly, identified, potent, dermatitis

Skin and percutaneous absorption:

• Stratum … is the …-limiting barrier to transdermal drug transport

  • Partially … tissue

  • 40% protein (keratin), 40% water, 20% lipids: triglycerides, fatty acids, cholesterols, phospholipids

• The rate of drug movement across stratum corneum depends on:

  • Drug …

  • Aqueous …

  • Partition coefficient

  • Drugs that have … aqueous and lipid solubility are preferred candidates

corneum, rate, nonliving, concentration, solubility, good

According to the Fick’s First Law of Diffusion, all of the following parameters affect the rate of drug transportation across a layer of skin, EXCEPT:

a. Diffusion coefficient

b. Drug concentration at the site of absorption

c. Thickness of the skin

d. Molecular weight of the drug

d

Solubility and percutaneous absorption:

• … solubility determines drug concentration at the absorption site

• MW, lipid solubility, drug ionization status, temperature, and skin hydration status determine the drug … coefficient, which affects the rate of transport across the membrane barriers

• Drugs penetrate the skin better in their … form

• … drugs cross the cell membrane through the lipid-rich region (transcellular route), whereas the … drugs favor transport between cells (intercellular route

Aqueous, diffusion, unionized, Nonpolar, polar

Other Preferred Factors for Percutaneous Absorption

• MW … (preferably <400) with adequate lipid and aqueous solubility

• Good hydration of skin

  • Patches can act as an … moisture barrier

• An application area with a … layer of skin

• A … application time

100-800, occlusive, thin, longer

All of the following factors favor percutaneous absorption of drugs, EXCEPT:

a. Longer time of application

b. Small drug molecular weight

c. Wet skin

d. A thick layer of stratum corneum

d

What are the 2 types of TDDS?

Membrane controlled systems and matrix of monolithic systems

5 major components of Membrane Controlled TDDS:

1. … liner (peel strip)

2. … layer

3. Rate controlling drug … membrane

4. Drug …

5. Outer …

Protective, Adhesive, release, reservoir, backing

Key points for the membrane controlled systems:

• What controls the release rate of drug from the reservoir?

  • Rate controlling …

• Where is an absorption enhancer added?

  • Drug …

• What are the functions of outer backing?

  • (a) … of the product;

  • (b) … of the drug and patient;

  • (c) … of the applied skin

• Drug should … the rate controlling membrane and adhesive layer, but … the protective liner and the outer backing

membrane, reservoir, Identification, Protection, Occlusion, permeate, not

Major components of Matrix (Monolithic) TDDS:

• Outer backing - … metal/plastic laminate

• Drug … matrix

• Two general designs with regards to the adhesive layer

  • May be a … around the drug matrix or the matrix itself may be …

impermeable, loaded, rim, adhesive

In a matrix transdermal system, the drug is including in what component?

a. Backing layer

b. Adhesive layer

c. Protective liner

d. All of the above

b

General clinical considerations in the use of TDDS:

• Press … in place with the hand for … seconds to ensure good contact

• Expect delayed onset and … effect

• Important to check … that patch is still in place

• Should not be … for dose adjustment

• Avoid touching the … layer with fingers when removing the protective lining

• Percutaneous absorption varies with the site of application. The preferred site is stated in the package insert for each product

  • … locations to prevent skin irritation.

• Applied to clean, intact, dry skin that is free of hair and not oily

  • … skin can accelerate drug permeation beyond the intended rate

  • … skin can impair adhesion of the patch

  • Removal of stratum corneum by wet-shaving can affect drug absorption rate

• Avoid using skin lotion at the application site

  • Skin lotion affects hydration of the skin and the drug absorption

• Patches can be left on when …, bathing or swimming (but avoid prolonged activity)

firmly, 30, prolonged, daily, cut, adhesive, Rotate, Wet, Oily, showering

Which of the following counseling points should be provided to patients taking fentanyl patch?

a. Evaluate pain relief in 3 h

b. Replace patch every day

c. Use the same application site to maintain consistent drug absorption

d. Apply patch to dry, flat and non-oily skin without hair

d