Transdermal Drug Delivery Flashcards
1
Q
Transdermal Drug Delivery (TDD) Advantages (5)
A
- Avoid GI tract problems - food interactions, stomach pH, substitute for oral (N/V)
- Avoid risks and inconvenience of parenteral delivery
- Identifiable in case of emergency or overdoses
- Avoids first-pass metabolism
- Improve patient compliance - multiple days treatment from 1 dose
PRESCRIBE FOR LONG TERM THERAPY
2
Q
TDD Disadvantages (4)
A
- Poor route for certain drugs - skin irritants or color
- Limited number of drugs can be administered this way - potency (limited range) and physical/chemical properties (lipophilic and size)
- Drug effects continue after patch is removed
- Difficult/expensive to develop
3
Q
Skin Features (6)
A
- Stratum Corneum
- Sweat pores and glands
- Epidermis - stratum corneum, squamous cell layer, and basal cell layer
- Dermis
- Hair shaft and follicle
- Fat layer
4
Q
Skin Layers (4)
A
- Surface - emulsified material of sebum, sweat, loose dead cells (thickness and composition vary)
- Epidermis - protect from external environment
- Dermis - mechanical function
- Subcutaneous fat - can be a drug depot
5
Q
Skin Appendages
A
- Blood vessels and nerves - from subcutaneous tissue to dermis
- Sweat glands - ducts rise from dermis through epidermis
- Sebaceous glands & hair follicles - extend to surface of skin
6
Q
Dermis
A
- 2-3 mm thick
- Matrix of tissue woven from collagen (strength & integrity) and elastin (elasticity)
7
Q
Dermis Blood Supply
A
- Temperature and body pressure regulation
- Delivers nutrients
- Remove metabolic waste products
- Reacts within 0.2 mm of skin surface - readily absorbs chemicals penetrating skin
8
Q
Epidermis Cell Types (4)
A
- Keratinocytes
- Melanocytes
- Merkel Cells
- Langerhans Cells
9
Q
Keratinocytes
A
- 90% of cells
- Protective sheath that repels pathogens and fluid loss
- Mitosis renews epidermis and top most layer is sloughed
- Main barriers to substances moving in and out of body
- Consists of 10-15 layers of flattened, keratinized cells stacked in highly organized fashion
- Cells align parallel to skin surface and lateral edges interdigitate with adjacent cells to create highly ordered lamina
10
Q
Stratum Corneum
A
- Composition - 50% proteins, 20% lipids, 30% water and water soluble compounds
- “Brick and Mortar Wall” configuration
- Protein = mainly keratin
- Lipids - ceramides, FFA, cholesterol, cholesterol esters
11
Q
3 Routes of Drug Penetration
A
- Intercellular
- Transcellular
- Transappendageal - via sweat glands or hair follicles
PATCH PLACEMENT HIGHLY AFFECTS ABSORPTION
12
Q
Skin Permeability Factors (3)
A
- Blood flow - Increased BF: Increased Absorption
- Disease - psoriasis, essential FA deficiency, atopic dry skin, etc.
- Age - thickness of skin remains same but the structural defects leads to wider cell junctions, lipid lamellae degradation, and increased transdermal H2O loss
13
Q
Drug Penetration
A
-Passive diffusion - requires concentration gradient
Factors affecting absorption:
- Drug concentration on skin
- Size of application area and exposure time
- Physicochemical drug properties (solubility, oil/water partition coefficient, molecular weight
- Thickness hydration of stratum corneum
14
Q
TDD Design Objectives (7)
A
- Physico-chemical properties to release drug
- Occlude skin so drug travels in ONE direction
- Adhere well to skin
- Adhesive/vehicle/drug should be non-irritating
- Consider size, appearance, placement of patch
- No bacterial growth beneath occluded skin
- Therapeutic advantage over other routes
15
Q
KNOW FOLLOWING PATCH STRUCTURES
A
- Liquid-filled Laminate Structure
- Solid-state Laminate Structure
- Drug in Adhesive Structure
- Foam Adhesive & Polymer Matrix
16
Q
Proper Use of TDD
A
- Apply to clean, dry skin
- Patch in contact with skin
- Skin should be hairless, NOT shaved
- Replacing patch - remove old patch, fold in half, and discard
- New patch - remove from sealed pouch, remove liner, place in different location
- Wash hands after handling
- NEVER cut patches, could cut drug
17
Q
Patch Precautions
A
- If patch pulls off, replace it, DON’T tape it
- Never use for immediate relief
- Patches may have drugs dissolved in alcohol (avoid use in alcoholics)
- Absorption varies depending on placement, wear at recommended sites and rotate them
- Condition of skin is important - adhesion, not broken, callused, irritated, hairy, or moisturized (can increase absorption)
18
Q
Transderm-Scop
A
- 1st transdermal product
- Contains Scopolamine - placed behind ear to treat motion sickness and delivers 1 mg per 3 days
- Scopolamine Attributes - potent, requires lowered plasma levels for therapeutic effects, adverse effects are minimized
19
Q
Nitroglycerin
A
- Potent and short half life
- Highly susceptible to first-pass metabolism
- Side effects at high concentrations
- Patches - prophylactic, delivers drug over 24 hours, reported in mg/h
- Nitro-Dur, Deponit, Transderm-Nitro, Nitrodisc, Minitran
20
Q
Nicotine
A
- Small, lipophillic, short half life
- Available in strengths of 28 mg, 21 mg, 14 mg, and 7 mg
- Cigarette delivers 1 mg of nicotine, depending on how much they smoke determines which patch they start on
- No short-term health risks with patch
- Nightmares and vivid dreams
- Patch users are 4x more likely to quit
21
Q
Transdermal Clonidine
A
- treats high blood pressure
- Potent, low dose, highly lipid soluble, chronic therapy
- Catapres-TTS - liquid filled laminate patch that delivers drug over 7 days
22
Q
Estrogen
A
- Hormone replacement therapy
- Potent, low dose, chronic therapy, first pass metabolism, stability in stomach
- Climara - 17B estradiol (natural), drug in adhesive and delivered for 1 week
23
Q
Ortho Evra
A
- Contraceptive, 20 cm^2 patch
- 3 layers - release liner, medicated adhesive layer, outer polyester protective layer
- Apply to butt, upper torso, outer/upper arm, lower abdomen ROTATE
- Bathe and swim as usual but do not oils, creams, or cosmetics on/around patch area
24
Q
Testosterone
A
Androderm
- Liquid-filled laminate
- Applied to back, abdomen, upper arm/thigh
- NOT applied to scrotum
Testoderm
- Solid-state laminate
- Apply to scrotal area
- Shave skin for optimal contact
25
Liposomes
- Spherical vesicle with membranes of phospholipids and cholesterol bilayer
- Encapsulated liquid solution inside that traps hydrophilic solutes that can't readily pass through lipids
- Hydrophobic drugs - dissolves into membrane
- Lipid bilayer fuses with other bilayers (in skin) to deliver liposome contents
26
Liposome Advantages and Disadvantages
Advantages
- Increases drug incorporation in stratum corneum
- Permeation enhancement
Disadvantages
- Aqueous
- Poor stability
- Hard to combine with patch technology
27
Transdermal Spray
Mechanism - reservoir formation on upper epidermis layer
| EX: Acrux
28
Spray Advantages (3)
1. Improved handling compared to semisolids
2. Improved dosing compared to semisolids
3. Less irritation potential compared to occlusive systems
29
Spray Disadvantages (3)
1. Limited application areas compared to gels/creams
2. Impact of showering, bathing, and swimming
3. Person to person contamination
30
Gels
Mechanisms
-Reservoir formation on upper epidermis layer
-Evaporation of solvents typically result in drug super saturation
EX: AndroGel (evaporation)
31
Gel Advantages (3)
1. Enlarged application area
2. Less irritation potential due to minimal occlusion
3. Virtually disappears after application
32
Gel Disadvantages (3)
1. Limited control of application area
2. Risk of contact contamination
3. Increased environmental risk where excessive drug is washed off
33
Penetration Enhancers
- Chemical agent that reversibly alters strat. corn. permeability
- Selection of enhancer - efficacy, lack of toxicity, component compatibility
**Both increase percutaneous absorption**
34
Mechanism of Enhancers (3)
1. Solvent action - directly solubilize tissue (skin components)
2. Interaction with intercellular lipids - disrupts highly ordered lamellar structure and increases diffusivity through membrane
3. Interaction with intracellular proteins - increases permeability through corneocytes
35
Thermal Transdermal Delivery
Mechanisms
-Increase permeability of stratum corneum
-Increase dermal blood perfusion
EX: CHADD
**Preferred application = local anesthetics and pain management**
36
Thermal Transdermal Advantages and Disadvantages
Advantages
- Shortening of lag time
- Increased permeability rates by 2-3x
Disadvantages
- Electrical heating requires large batteries
- Chemical heating only lasts a one-day period
37
Heat Provides... (5)
1. Increased solubility for most drugs
2. Increased permeability
3. Increased fluid circulation
4. Vessel Dilation
5. Increased release rate of drug from local skin tissue to systemic circulation
38
Sonophoresis Mech/Advantages/Disadvantages
Mech - Disordering of lipid bilayer (Increase gapping)
Advantages
- Shortens lag time
- Transdermal application of peptides, proteins, and other macromolecules become feasible
Disadvantages
- Limited or no mobility due to systemic size and energy requirements
- Skin irritation above certain energy levels and durations
**Applications = local anesthetics, pain management, and body fluid monitoring**
39
Iontophoresis
- Physical method to increase transdermal delivery
- Electrical current used both locally and systemically to cause reversible changes in morphology/permeability
- Delivers ionized species and high MW drugs (proteins and peptides)
- Drug reservoir (+) and return reservoir-saline (-)
EX: E-TRANS
40
Microfabricated Microneedles
- Needles - long enough to penetrate strat. corn. (10-15 um) but doesn't stimulate nerves
- Increases permeability and can deliver high MW drugs (proteins and peptides)
**epidermal microstructure tech = under development**
41
MicroScrub
- Strat. corn. removed by rubbing directly over skin
| - Unique design allows for finite limit of cell removal to prevent excess abration
42
Power Injection Systems
- Dry powder particles - diameter = 1-75 um, stable, high doses
- Released at high velocities to penetrate skin - helium - propellant
- NO MW LIMITS - used for vaccines, DNA, etc.
- Generates "fluid needle" that can be calibrated for injection depth
EX: PharmaJet, liquid needle system
