4 - Transdermal Flashcards
How is px compliance achieved through the transdermal dosage form?
- Application convenience
- Proven results
- Product recognition
Do transdermal drug substances only exert pharmacological effects locally?
No, can exert locally and systemically depending on what kind of therapeutic regimen is prescribed
___ molecules cannot be delivered through transdermal administration
Large
Do drugs undergo first pass metabolism when administered through the percutaneous route?
No
What is the onset of drug action for transdermal drugs?
- Very slow
- May have wide variations among different px due to skin conditions and application approaches
When are transdermal dosage forms generally used and when can they NOT be used?
- Generally used for concentration maintenance and management in long-term therapies
- Can’t be used for emergency situations
What is advantageous about skin as a dosage route?
- Accessible
- Large surface area
- Tolerance to variety of substances
- Convenience
What makes topical preparations appealing to px?
- Wide choice of products
- Minimal systemic absorption
- Individualized amount/method
- Direct site application
What are characteristics of ointments?
- Long contact time
- Used on dry sites
- Greasy
- Poor drug medium
- Contain dissolved or suspended drug components
Why can’t ointments be used on moist sites?
Greasy and lipophilic components are water-insoluble/immiscible
Why has the use of ointments gradually decreased?
- Can stain clothing
- Difficult to clean after application
What are characteristics of creams/lotions?
- Good drug medium
- Large drug loading capability
- Rinsable
- Can be applied to both dry and wet sites
What are the 2 types of lotions/creams available? Why is used more often and why?
- Water-in-oil (W/O)
- Oil-in-water (O/W)
- O/W used more often b/c non-greasy, rinsable, and good for most topical skin purposes
What are some characteristics of gels?
- Lubricating
- Large drug loading capability
- Washable
- Transparent
What are some characteristics of pastes?
- Provide protective barrier
- Moisture absorption
- Wet sites
- Non-greasy
Pastes are basically ointments with ____
A high percentage of insoluble particulate solid
Why do pastes make a good protective barrier?
- Form unbroken film
- Absorb moisture
- Neutralize noxious chemicals
Are pastes or ointments less greasy? Why?
Pastes b/c adsorb fluid hydrocarbon fraction to particulates
What are common oil base excipients used in transdermal products?
- Wax
- Petrolatum
- PEGs
- Stearyl alcohol
What are common aqueous base excipients used in transdermal products?
- Water
- Polymers
What are common viscosity-adjusting excipients used in transdermal products?
- Propylene glycol
- Glycerin
- PEGs
- Polymers
What are common emulsifying excipients used in transdermal products?
Surfactants (O/W or W/O)
Do transdermal products generally contain preservatives?
Yes
What are the basic steps of manufacturing a transdermal product?
- Heating
- Mixing
- Incorporating some medication(s)
What is tested for quality control of transdermal products?
- Drug content
- pH
- Alcohol content
- Viscosity
- Preservation
- Minimum fill
Patch has ___% more/less absorption than a tablet. What does this cause?
- 60% more
- Greater chance of adverse effects
What are some ways that the transdermal dosage form improves drug absorption?
- Providers uniform and predictable plasma concentrations
- No first-pass metabolism
- Improved bioavailability
- Prolonged drug effect and duration
- Reduced administration frequency and adverse effects
Which transdermal products produce local effects?
- Cosmetics
- Consumer-care products (ex: sunscreen, muscle relaxing cream)
- Certain medications
Which transdermal products produce systemic effects?
Most patches
What is the general structure of skin?
- Epidermis (stratum corneum and stratum germinativum)
- Dermis
- Subcutaneous fat tissue
What is the function of skin?
- Retain body fluids/tissues
- Prevent foreign invasions
- Feel external senses (heat, cold, pain, pressure)
- Absorb external attacks
- Regulate body temp and BP
Which portion of skin controls the rate of drug penetration and absorption?
Stratum corneum
What kind of cells are found in the stratum corneum?
- Inactive
- Compacted, dehydrated, keratinized, and replenished
What is found in the dermis?
- Living cells
- Blood vessels
- Nerve sensors
- Lymphatics
What are the functions of the subcutaneous fat tissue?
- Temp control
- Shock absorber
- Other protection
- Store energy
What is found in the skin appendages?
- Hair follicles
- Various glands
What is the function of skin appendages?
Metabolism
Does drug absorption change based on the area of skin?
Yes
Should transdermal patches be applied to palms or soles?
No, skin is very thick so minimal absorption will occur
What are some factors that affect drug absorption of a transdermal product?
- Application site
- Skin humidity
- Environment conditions
- Skin health
- Drug properties
- Formulation properties
- Other (age, gender, race)
Dry skin can ____ drug permeation through the skin
Reduce
What can be done to improve drug absorption on dry skin?
Use occlusive wrappings to minimize water loss
Broken skin allows for ____ permeability
Increased
Irritation and mild trauma to skin ___ permeability
Increases
Does permeability of skin differ btwn genders?
No
How does race affect drug absorption through the transdermal route?
Black skin has more cell layers and is denser than white skin, thus showing less permeability
What is the relationship btwn permeation rate and diffusivity?
Direct relationship (low permeation rate = low diffusivity)
Which sites of the body have low permeation rates?
- Back
- Forearm
- Abdomen
- Back of hand
What are the normal sites to apply a transdermal product? Why?
- Arms, chest, thighs
- Easy access, less hair, high tolerance, and invisibility
How does humidity increase penetration and absorption?
- Pulls drug out of preparation
- Increases contact w/ stratum corneum
- Solubilizes drug and stratum corneum
Why does high temp increase penetration and absorption?
- Increases drug diffusivity
- Increases blood circulation
- Increases skin hydration
What effect does damaged skin have on the PK of a transdermal product?
- More secretion
- More circulation
- More metabolism
- High permeability
For transdermal products, are lipophilic or hydrophilic drugs preferred? Why?
- Lipophilic
- Can partition more easily into skin components, most of which are lipophilic
For transdermal products, are small or large molecules preferred?
Small
What is the recommend dose of a transdermal product?
- Less than 20 mg/day
- Dosing once daily or weekly
What is the recommend half life of a transdermal product?
Less than 10 hours
What is the recommend molecular weight of a transdermal product?
Less than 400
What is the recommend therapeutic index of a transdermal product?
Low
What occurs in a permeation transdermal drug delivery system?
Drug reservoir sandiwched btwn drug-impermeable backing and rate-controlling polymeric membrane
What can the drug reservoir be in a permeation transdermal drug delivery system?
- Solid polymer matrix
- Semisolid suspension
- Solution
What can the rate-controlling membrane by in a permeation transdermal drug delivery system?
- Microporous
- Non-porous polymer w/ specific drug permeability
How can drug release rate be controlled w/ a permeation transdermal drug delivery system?
- Varying composition of drug reservoir formulation
- Varying permeability coefficient
- Varying thickness of rate-controlling membrane
What occurs in a diffusion transdermal drug delivery system?
- Active ingredient homogeneously dispersed in hydrophilic or lipophilic polymer matrix
- Medicated polymer is molded into a disk, which is then applied to a patch
How can drug release rate be controlled w/ a diffusion transdermal drug delivery system?
- Initial drug loading dose
- Drug solubility and diffusivity in matrix
In a diffusion transdermal drug delivery system, what is the drug release amount proportional to?
Square root of time
A dispersion transdermal drug delivery system is considered a hybrid of _____ and _____
Permeation and diffusion dispersion systems
What occurs in a dissolution transdermal drug delivery system?
- Drug reservoir is formed by suspending drug solids in aqueous solution of water-miscible solubilizer
- Suspension then homogeneously dispersed in lipophilic polymer
How can drug release rate be controlled w/ a dissolution transdermal drug delivery system?
- Drug solubility in microreservoirs and polymer matrix
- Drug partition and diffusivity in polymer matrix
In a gradient transdermal drug delivery system, drug release follows ___ order kinetics
Zero
What is the recommended shelf life for transdermal products?
Up to 2 years
What is tested in in vitro evaluation of transdermal products?
- Drug release from preparations
- Drug penetration across skin
- Simulation of in vivo conditions
- Diffusion cells and membranes
What is tested in in vivo evaluation of transdermal products?
- Drug concentration in blood
- PK/PD parameters
What are the objectives of a transdermal drug delivery system?
- Avoid IV administration
- Bypass oral variations in drug absorption and metabolism
- Achieve prolonged drug effects
- Reduce first-pass metabolism
- Increase overall bioavailability
- Program drug release rate
- Improve px compliance
What can be physically done to optimize transdermal drug delivery?
- Skin stripping (strip stratum corneum)
- Skin hydration
- Iontophoresis
- Skin heating
What can be done chemically to optimize transdermal drug delivery?
- Lipophilic analogs
- Skin delipidization
- Skin penetration enhancers
What can be done biochemically to optimize transdermal drug delivery?
- Prodrugs
- Skin metabolism inhibitors
What do skin metabolism inhibitors do?
Increase amount of drug reaching deeper sites or systemic circulation
What is iontophoresis?
Facilitates transport of ionic species through skin layers by applying a physiological acceptable electrical current
What is iontophoresis especially beneficial for?
Protein and peptide drug candidates
What is electroporation? Does it work on skin membranes or on the drug?
- Application of electric field to living cells to form transient pores for increased permeability
- Works on skin membranes
What is sonophoresis? Does it work on skin membranes or on the drug?
- Use of ultrasound to enhance drug permeation across skin
- Works on skin membranes
What are the mechanisms used to enhance permeation?
- Increase solubility in stratum corneum
- Reduce diffusion barrier of stratum corneum
- Facilitate drug partition into skin
- Amplify drug transport through appendages
- Promote drug partition at stratum corneum
What are advantages to prodrugs?
- Improve penetration
- Minimize metabolism
What are microneedles used for?
Delivering proteins and peptides
