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?