EMAC 276 Brian Cheung, Connie Chien, Corinne Nelson, Michelle Song, Xiaoxin (Shawn) Zhu.

Polymers for Transdermal Delivery

Systems

EMAC 276Brian Cheung, Connie Chien, Corinne

Nelson, Michelle Song, Xiaoxin (Shawn) Zhu

History

• First approved in 1979

• 3-day patch for motion sickness in astronauts

• Became popular in 1990s with nicotine patch

• Currently used for birth control, glucose monitoring, local anesthesia, etc

Mechanism

- only a couple hundred Daltons

- heavily favor lipids and require doses of milligrams per day or less

- hard for hydrophilic drugs to pass through

Components of TDD

• Matrix-formers

• Permeation enhancers

• Rate-controlling membrane

• Pressure-sensitive adhesives (PSAs)

• Backing laminate

• Release liner

Requirements for Rate Controlling Membrane1. Biocompatible

2. Highly dependent on the solubility of drug

3. Easy control of composition and thickness

Polymeric Materials for Rate Controlling Membrane

Ethylene-Vinyl Acetate (EVA)

• Permeability can be altered by adjusting vinyl-acetate content

• VA group leads to better solubility and diffusivity of polar groups

• Cost of Material: $1.6-1.7 per kilogram

Polymeric Materials for Rate Controlling Membrane

Silicone Rubber:

• Good Biocompatibility, ease of fabrication

• Free rotation around silicone rubber backbone induce high permeability

• Cost of Material: $4.8-5.5 per kilogram

http://www.pharmtech.com/pharmtech/data/articlestandard/pharmtech/192002/18600/article.pdf

Polymeric Materials for Rate Controlling MembranePolyurethanes:

• Condensation of polyisocyanates and polyols

• PU is suitable for hydrophilic polar compounds

• Cost of Material: $2.2-2.5 per kilogram

http://upload.wikimedia.org/wikipedia/commons/c/ca/Polyurethane.png

Natural Polymer for Rate-Controlling Membranes - Chitosan

Natural polymers can potentially reduce the skin irritation or allergic reactions induced by synthetic polymers

Formed by deacetylation of chitin

Thacharodi, D., and K. P. Rao. "Development and in Vitro Evaluation of Chitosan-based Transdermal Drug Delivery Systems for the Controlled Delivery of Propranolol Hydrochloride." Biomaterials 16 (1995): 145-48. Web. 8 Apr. 2012. <http://ac.els-cdn.com/014296129598278M/1-s2.0-014296129598278M-main.pdf?_tid=e7b31de07a5a1327b75f97ed19d36784&acdnat=1333947017_b278c0e1000399a40ac69074daeac121>.

Requirements for PSAs

1. Adhere easily2. Permanently tacky3. Does not cause instability of the

a. drugb. enhancer, andc. adhesive

4. Does not leave residue when peeled off

Polymeric Materials in Pressure Sensitive Adhesives

Polyisobutylene:

• Mix of low and high molecular weights

• Fillers are used for reinforcement, reducing viscosity and cost

• Cost of Material: $1-100 per kilogram

http://www.pharmtech.com/pharmtech/data/articlestandard/pharmtech/192002/18600/article.pdf

Polymeric Materials in Pressure Sensitive Adhesives

Polyacrylates:

• Amorphous and water-clear color in solution

• Stability toward aging

• Great resistance to acidic and alkaline hydrolysis and UV degradation

• Cost of Material: $3.2-4.5 per kilogram

http://www.pharmtech.com/pharmtech/data/articlestandard/pharmtech/192002/18600/article.pdf

Polymeric Materials in Pressure Sensitive Adhesives

Silicones:

• Stable adhesive in throughout a wide range of temperature (-73 to 250C)

• Outstanding combination of bicompatibility and ease of fabrication for hydrophilic drugs

• Poor solubility, permeability and releasing property

• Cost of Material: $6.2-8.3 per kilogram

• http://www.pharmtech.com/pharmtech/data/articlestandard/pharmtech/192002/18600/article.pdf

• Layer of protective material• Chemical Resistance is the most important

factor• It keeps the medication from seeping out of the

patch

• Good chemical resistance:• Low modulus• High flexibility• Good oxygen transmission• High moisture vapor transmission rate

Laminates

• Relatively Inert

• Increase hydration of the skin

• Make sure that any polymers used do not irritate the skin

Requirements for Laminates

Polymers used for Laminate

Polyethylene

Vinyl

Polyester

• Protects the skin contacting adhesive• It is removed immediately before being

placed on the skin• More a part of the packaging material than

the actual patch itself• Made of Polyethylene or PVC and Silicone

or Teflon• Cross linking may occur

• Increase force to remove liner from patch

Release Liner

Silicone

Teflon

PVC

Problems

• Only small-sized molecules delivery (very thick stratum corneum)

• Difficult balancing the degree of damage and penetration

Future development

• Electroporation

• Cavitational ultrasound

• Thermal ablation

• Microdermabrasion

• Biochemical enhancer

• Chemical enhancer combination

• Microneedles

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700785/

Chemical enhancer combination

SLS + phenyl piperazine

+

http://en.wikipedia.org/

Microneedles

S. H. Bariya, M. C. Gohel, T. A. Mehta, and O. P. Sharma, "Microneedles: An Emerging Transdermal Drug Delivery System," Journal of Pharmacy and Pharmacology, 64(1), 11-29 (2012).

Questions?