transdermal Flashcards
What are the advantages and disadvantages of transdermal drug delivery?
- Advantage
- Avoids GI drug absorption difficulties
- Alternative to oral or parenteral administration
- Avoids first-pass metabolism
- Multi-day therapy can be achieved by a single application • Extends the activity of drugs with short half-lives
- Easy to terminate the drug’s effect
- Disadvantages
- Unsuitable for drugs that sensitize the skin
- Only relatively potent drugs can be used
- Adhesion of the transdermal delivery system to the skin may be variable
What is the main pharmacokinetic advantage of transdermal delivery?
- Provides sustained delivery of drug over a long period of time from a single dose (compared to oral dosing)
- avoids the peak-and valley concentration increase and decrease
- Keeps drug level within MEC and MTC
- Avoids the first pass effect
What kind of drugs are good candidates for transdermal delivery?
Drugs with high potency (dose requirement of less than 25 mg/day) Short half-life (< 10h)
Low molecular weight
Lipophilic
Low melting point
High skin permeability
(>0.5x10-3 cm/h)
Non-irritating and
non-sensitizing to skin
Low oral bioavailability
Low therapeutic index (i.e., requires tight control of plasma levels)
Ideal parameters for candidates
- lipophilicity (oil/water partition coefficient 10-1000 ie. log P 1-3)
- molecular weight < 500
- melting point < 200C
- pH of saturated aqueous solution 5-9
- deliverable dose < 10 mg/day
What are the requirements for transdermal patches?
Shelf-life up to 2 years 2
Small patch size ( eg. < 40 cm )
Convenient dose frequency (eg. 1/day, 1/week)
Adequate skin adhesion
No residue (i.e. cold flow around the edges in storage or after application to skin)
Reliable and consistent drug delivery in patients
No dermal reactions (contact dermatitis, skin sensitization, erythema, maceration, irritation) Cosmetically appealing and easy to use
What type of transdermal patches do you know and what are their properties?
- Reservoir tpe with rate controlling membrane
- matrix type
- drug in matrix
- or adhesive on perimeter or on entire surface
- durg in adhesive
- monolithic or multilaminate
What are the components of a transdermal patch?
Backing film
Rate-controlling membrane
Drug matrix or vehicle (including permeation enhancers, stabilizers, antioxidants, solvents) Pressure sensitive adhesives (PSA)
Release liner
What are the rate controlling mechanisms in the following transdermal patches?
Reservoir type patch – rate controlling membrane
Matrix patch – rate controlling matrix and stratum corneum
DIA patch – rate controlling adhesive matrix
What are the advantageous properties of DIA type patches with regards to dosing, comfort to patient and control of delivery?
Extremely comfortable
Patch is very thin
Maximum use of surface area of the patch
No membrane
Patch can be cut to adjust dose
frist order kinetics for release 0> propotional to drug conc within adhesive
*whe drug conc in adhesive falls, constant drug delivery profile is diff to maintain -> use multilaminate design
What are the main safety issues with patches?
- confusion: dsign, dose strengh, freq of admin
- improper application
- peeling not only proective layer but also adhesive overlay
- applying over old patches not directly to skin
- protective liner not removed
- location for application
- must remove old patch
- monencalture
- dosing terms confusing
- TTS = Transdermal Therapeutic System, NOT Tuesday, Thursday, Saturday
- dosign intervals
- could be daily, every 3 days, weekly, every 3 weeks etc
- could forget where old patch is is enough time goes by
- pediatic patch isses
- cutting them not possible with reservoir types, only possible with matrix or DIA
- Safe storage
- accidental ingestion?
rules for patch application and instructions for patients?
Apply on non-hairy areas (may require hair clipping)
Site of application should be dry —> don’t use in sauna or hot, humid place Remove old patch before applying new patch
Do not apply to areas with cuts or skin damage
Do not apply below the knee or elbow
Explain why fentanyl is a good candidate drug for transdermal delivery.
highly potent
molecular weight of fentanyl base is 336.5,
n-octanol:water partition coefficient is 860:1 pKa is 8.4.
What type of fentanyl TTS are available and what is the importance from safety point of view?
All three main types of patch designs are available;
reservoir patches can puncture and dose dumping can occur which can cause overdose and respiratory failur
Discuss medication safety issues with fentanyl patches.
- potential harm
- Fatalities due to inappropriate prescribing, dispensing and administration: wrong dose, strength or quantity
- ssues related to designa nd packaging
- translucent appearance makes it difficult to locate patches on the body
- Poor adhesion can cause loss of patch
- Non-uniformity of dosing expressions on packaging
- Residual drug in disposed patches can lead to abuse
- accidental exposure to a skin patch containing fentanyl can be deadly , especially in children
What is the rationale for using DTS and what type of DTS do you know?
Maximize delivery into the stratum corneum, upper epidermis or dermis, while minimizing further absorption through the skin into the systemic circulation
*used for local dermatiologial conditions
- > more uniform delivery (local anesthetics)
- > during duration (retined in stratum corneum longer)
- > substantivity (resistant to washing off during showering, swimming)
- > deeper peneration
- dec side effects
