Matrix Dispersion Systems in Transdermal Drug Delivery

Samantha Sarett, Kristina Vaci, Kyle Householder, and Si Young An

Transdermal Drug Delivery Systems (TDDS)

• Distributes a drug through the skin and directly into the bloodstream

• Avoids first pass effect

Types of TDDS

• Reservoir System• Matrix System• Microreservoir System

Matrix System• Four Layers

– Backing Layer– Drug Reservoir/Drug in Matrix– Adhesive Layer– Release Liner

• Rate of drug release is controlled by diffusion through and erosion of the matrix

Matrix Former

• Properties necessary– Release properties– Adhesion–cohesion balance– Physicochemical properties– Compatibility and stability with other components of the

system as well as with the skin

Poly(ethylene glycol)

• PDI value of 1.01• High solubility in organic solvents• Soluble in water • Low intrinsic toxicity

Cross-linked poly(ethylene glycol) (PEG) networks

• PEGs cross-linked with tris(6-isocyanatohexyl) isocyanurate by means of a urethane–allophanate bond

• capable of swelling in phosphate-buffered saline or ethanol and forming gels.

• release the solutes (proteins) in a biphasic manner.

Disadvantages

• Non-biodegradability• Oxidative degradation• Molar mass matters

• Overcoming drawbacks of using PEG– Use of biodegradable polymers (e.g. PLA, PGA,

PLGA)

HPMC

• Hydroxypropyl methylcellulose (HPMC) is a matrix former

Pulp cellulose + caustic soda Alkali-cellulose complex+ Methyl chloride + Propylene oxide HPMC

HPMC

• K grade, E grade, and F grade• K: 19-24% methoxy substitution, 7-12%

hydroxypropyl substitution, Tg = 70oC• E: 28-30% methoxy substitution, 7-12%

hydroxypropyl substitution, Tg = 56oC• Degree of polymerization of 100 to 1,500• Molecular weight varies

HPMC

• Erosion occurs as the outer layer of the matrix is diluted by water to a disentanglement concentration

Water diffuses into the matrix glassy matrix

to rubbery

Drug is released from the swollen system; eventually it erodes

HPMC

• Used to deliver:– Enalapril maleate; hypertension– Propanolol; beta-blocker– Repaglinide; diabetes mellitus

Ethyl Cellulose

• Hydrophobic and Lipophilic

Ethyl Cellulose

• Addition of polyvinylpyrrolidone PVP• Addition of dibutyl phthalate• Tg= 129°C• Good Compatibility

Adhesive Layer

Properties:• Good Permeation Rate• Biocombatible with the

skin• Tacky• Chemically cohesive with

drug• Water Resistant • Resistant to degradation

Acrylic Acid • Chemical Structure

Fabrication• Synthesize in organic solvent at a boiling point temperature around

77˚C• Add in monomers for 1 hour, then let reaction go for 7 hours• Cast on to release liner with silicone• Set to dry and laminate back for application

Acrylic Acid

• Mechanical Properties• Low Tg and amorphous• Resistant to oxidative and UV degradation• Water Resistant• Good gas permeation• Compatible with several drugs including:

– Nicotine– Estradiol– nitroglycerine

Other Adhesive Polymers

PolyIsobutylene• Good Low Temperature Properties

Silicones• Very easily modified

References• Cho, Y.J, Choi, H.K. “Enhancement of percutaneous absorption of ketoprofen: effect of vehicles and adhesive matrix.”

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References

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• Arora, P. and Mukherjee, B.  “Design, development, physicochemical, and in vitro and in vivoevaluation of transdermal patches containing diclofenac diethylammonium salt.” J. Pharm. Sci., 91: 2076–2089. doi: 10.1002/jps.10200

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