Transdermal Drug Delivery Systems Flashcards
Transdermal Drug Delivery Systems (TDDS)
Facilitate the passage of therapeutic quantities of drug substances through the skin and into the general circulation for their systemic effects
Transdermal Drug Delivery
API should migrate through the skin to the underlying blood supply without building up in the dermal layers
Topical Drug Delivery
API should reside in the skin, which is the target organ
Stratum Corneum
10- to 15-µm-thick layer of flat, partially desiccated nonliving tissue
Composition of stratum corneum
~40% protein
~40% water
~20% lipid
Lipid content
1) is concentrated in the extracellular phase of the stratum corneum and largely forms the membrane surrounding the cells
2) Because a major route of drug penetration is through the intercellular channels, the lipid component is considered an important determinant in the first step of absorption
When does drug becomes available for absorption into the general circulation
when it reaches the vascularized dermal layer
Advantages of TDDS
1) Bypass hepatic “first-pass” and gastrointestinal incompatibility
2) Reduce side effects due to the optimization of the blood concentration-time profile
3) Provide predictable and extended duration of activity
4) Greater patient compliance due to the elimination of multiple dosing schedules
5) Reversibility of drug delivery
Disadvantages of TDDS
1) Only relatively potent drugs are suitable candidates
2) Contact dermatitis
TDDS shelf life
up to 2 years
TDDS patch size
< 40 cm2
TDDS dose frequency
once a day to once a week
TDDS aesthetic appeal
clear, tan, or white color
TDDS packaging
Easy removal of release liner and minimum number of steps required to apply
TDDS skin adhesion
Does not fall-off during dosing
TDDS skin reactions
Nonirritating and nonsensitizing
TDDS Drug release
Consistent pharmacokinetic and pharmacodynamic profiles over time
Factors Affecting Percutaneous Absorption ( listen to lec cap)
1) Drug concentration
2) Area of application
3) Lipophilic:Hydrophilic solubilities
4) Molecular weight
5) Skin hydration, needs to be dry
6) Skin thickness
7) Exposure time
Percutaneous Absorption Enhancers: Chemical enhancers
1) increase skin permeability by reversibly damaging or altering the physicochemical nature of the stratum corneum to reduce its diffusional resistance
2) Increased hydration of the stratum corneum
and/or
3) A change in the structure of the lipids and lipoproteins in the intercellular channels through solvent action or denaturation
Percutaneous Absorption Enhancers chemical enhancers’ selection is based on?
efficacy, low dermal toxicity and compatibility with other components
chemical enhancers example
Acetone Azone Dimethyl sulfoxide (DMSO) Ethanol Oleic acid Polyethylene glycol Propylene glycol Sodium lauryl sulfate
Iontophoresis
delivery of a charged chemical compound across the skin membrane using an electrical field
Sonophoresis
high frequency ultrasound to enhance transdermal drug delivery
Monolithic systems
1) incorporate a drug matrix layer between backing and frontal layers
2) Drug is dispersed in a matrix layer composed of a polymeric material which controls the rate of drug release
Monolithic TDDS matrix preparation
Matrix may be prepared either with or without an excess of drug with regard to its equilibrium solubility and steady-state concentration gradient at the stratum corneum.
Monolithic TDDS are designed to contain
an excess of drug and thus have drug-releasing capacity beyond the time frame recommended for replacement ensuring continuous drug availability and absorption as used TDDSs are replaced on schedule with fresh ones.
Membrane-Controlled TDDS
contain a drug reservoir or pouch, a rate controlling membrane, and backing, adhesive and protective layers
How the release rate of drug through the controlling membrane remains
As long as the drug solution in the reservoir remains saturated
Why A small quantity of drug is frequently placed in the adhesive layer ?
to initiate prompt drug absorption and pharmacotherapeutic effects upon placement on the skin
If the drug is delivered to the stratum corneum at a rate less than the absorption capacity,
the device is the rate-controlling factor
If the drug is delivered to the skin area to saturation
the skin is the rate-controlling factor
Absorption
may vary with the site of application.
TDDSs should be applied to
clean, dry skin that is relatively free of hair and not oily, irritated, inflamed, broken, or callused
Use of skin lotion
should be avoided at the application site.
TDDSs should not be physically
altered by cutting.
How A TDDS should be removed from its protective package,
with care not to tear or cut into the unit.
Place at a site that will
not subject it to being rubbed off by clothing or movement
Wear for the full period stated in the product’s instructions
then remove and replace with a fresh system as directed
Cleanse hands thoroughly before and after applying a TDDS and do not
rub eyes or touch the mouth during handling of the system
if there is sensitivity or intolerance to a TDDS or if undue skin irritation results
Seek reevaluation
Used TDDS should be folded in half with the adhesive layer together and reused or not?
not to be reused
