Lecture 6 Transdermal Drug Delivery Flashcards
What is a Transdermal Drug Delivery System (TDDS)?
A system that facilitates the passage of therapeutic quantities of drug substances through the skin and into the general circulation for their systemic effects.
What are the advantages of TDDS?
Bypass hepatic “first-pass” and gastrointestinal incompatibility
Reduce side effects due to the optimization of the blood concentration time profile
Provide predictable and extended duration of activity
Greater patient compliance due to the elimination of multiple dosing schedules.
Enhance therapeutic efficacy
Reduce frequency of dosage
Reversibility of drug delivery, which would allow for removal of the drug source
Minimize inter/intra-patient variation
Self-administration
What are the disadvantages of TDDS?
Only relatively potent drugs are suitable candidates
Contact dermatitis
What is the ideal shelf life for a TDDS?
up to 2 years
What is the ideal patch size for a TDDS?
Patch size less than 40 cm2
What is the ideal dose frequency for a TDDS?
Once a day to once a week
What is the ideal aesthetic properties for a TDDS?
Clear, tan or white color
What is the ideal packaging for a TDDS?
Easy removal of release liner and minimum number of steps required to apply
What is the ideal skin adhesion properties for a TDDS?
no fall-off during dosing
What is the ideal skin interactions for a TDDS?
Nonirritating and nonsensitizing
What is the ideal drug release for a TDDS?
Consistent pharmacokinetic and pharmacodynamics profiles over time.
What are the factors that affect percutaneous absorption?
Drug concentration, surface area, lipophilic: hydrophilic solubilities, Molecular weight, skin hydration, skin thickness, exposure time
What is the equation that helps determine the diffusion of drugs across the skin?
J = (KDscCs)/hsc J = transdermal flux K = skin-vehicle partition coefficient Dsc = effective diffusion coefficient Cs = saturation concentration of the drug hsc = effective thickness of the stratum corneum
What are the percutaneous absorption enhancers?
Chemical enhancers
Iontophoresis
Sonophoresis
What do chemical absorption enhancers do?
Increase skin permeability by reversibly damaging or altering the physicochemical nature of the stratum corneum to reduce its diffusional resistance. Increased hydration of the stratum corneum and/or A change in the structure of the lipids and lipoproteins in the intercellular channels through solvent action or denaturation.
How do you select a percutaneous absorption enhancer?
Selection is based on efficacy, low dermal toxicity and compatibility with other components.
What are the examples of chemical enhancers that can be used?
Acetone, Azone, Dimethyl sulfoxide(DMSO), Ethanol, Oleic acid, Polyethylene glycol, propylene glycol, sodium lauryl sulfate.
What is Iontophoresis?
Delivery of a charged chemical compound across the skin membrane using an electrical field.
What is sonophoresis?
High frequency ultrasound to enhance transdermal drug delivery.
What is a monolithic TDDS?
Monolithic systems incorporate a drug matrix layer between backing and frontal layers.
What is a membrane-controlled TDDS?
Membrane controlled systems contain a drug reservoir or pouch, a rate controlling membrane, and backing, adhesive and protective layers.
How can you determine if a device is rate-controlled or not?
If the drug is delivered to the stratum corneum at a rate less than the absorption capacity than it has a device that is rate-controlling.
When is the skin the rate-controlling factor?
If the drug is delivered to the skin area to saturation, the skin is the rate-controlling factor.
What clinical considerations need to be made concerning TDDS?
Site of application Clean, dry skin Avoid lotion, etc. Do not physically alter Do not tear or cut; remove carefully Place where it will not be rubbed off Wear for the full time period Clean hands before and after application If irritation results, remove TDDS Upon removal, fold so adhesive layers touch and seal and discard properly
What type of quality control should be done on TDDS?
Stability of the assembled system
Release profile
In vitro assessment of TDDS using diffusion cells
In vivo assessment of TDDS
