PDD 13: Transdermal Drug Delivery Flashcards
What is transdermal drug delivery?
delivery of drugs from the surface of the skin through the various layers into the systemic circulation
What is the transdermal delivery system?
drug delivery system that supports the passage of a drug through the skin and into the systemic circulation
- typically transdermal patches
What are the advantages of transdermal drug delivery?
avoids variables that PO drugs are subjected to:
- pH (degradation, ionization)
- enzymatic degradation and first-pass metabolism
- gastric emptying time
- interactions with food/drink and other PO drugs
avoids the risks and inconveniences of parenteral therapy
- risk of infection
- fear and pain
- need for trained professionals
- hazardous waste/disease transmission
possess the benefits of controlled drug delivery
- reduced dosing frequency
- reduced blood level fluctuations
- reduced sub-therapeutic dosing
- reduced systemic side-effects
- extends utility of drug with short t1/2
therapy can be stopped by removal of the system
- removal of the system will result in immediate discontinuation of drug input
- results in gradual decline of the drug concentration in blood
easily identified for dosing and emergency purposes
- many systems have identifying markings but many are clear for aesthetic reasons
Not all drugs are viable candidates for TDD. There needs to be good therapeutic rationale, and therefore not good for…
- drugs with good PO bioavailability and infrequent dosing that are well-accepted by patients
- drugs needing large and rapid bolus dosing
- tolerance-inducing drugs
- drugs requiring chrono-pharmacological management (ie. pulsatile administration)
What properties should drugs ideally have for transdermal delivery?
- logP between 1-3
- MW under 600 Da
- high biological activity
- and not cause skin irritation
What are the general characteristics of transdermal DDS?
- two major designs of transdermal ‘patch’ systems
- patch size controls dose delivered and therefore the amount of drug absorbed – patches are made in different sizes for different doses
- patches should always be applied to clean, dry, non-hairy sites
What are the 2 major designs of transdermal ‘patch’ systems?
- membrane-controlled (or reservoir) systems
- matrix systems
(both systems provide controlled release of encapsulated drug over long periods of time)
Is the application site of patches constant?
yes – depending on what the system is used for
- typically use upper back (shoulder), upper arm
- vivelle - lower abdomen
- minitran – chest
- do not use lower arm or lower legs
- if need to remove hair – clip don’t shave
- no moisturizers or lotions
What are the 5 major components of membrane-controlled transdermal DDS?
- outer backing – impermeable metal/plastic laminate
- drug reservoir
- rate controlling membrane
- adhesive layer
- release liner
Membrane-Controlled Transdermal DDS Components
What is the purpose of the outer backing?
protection of the patient and the drug, and provides identification of the medication and system
- occlusive to prevent the transmission of water vapour
- impermeable to the penetration of drug
- typically made of poly(ethylene) terephthalate sometimes laminated to thin metal foil
Membrane-Controlled Transdermal DDS Components
What is the purpose of the drug reservoir?
holds the drug dispersion
Membrane-Controlled Transdermal DDS Components
What is the drug reservoir composed of?
composed of solid drug particles dispersed in:
- viscous liquid silicon fluid (Transderm Nitro)
- gel – poly(acrylic acid) (Estraderm)
- solid polymer (polyisobutylene) (Transderm V)
- may contain a penetration enhancer (ethanol or surfactant)
Membrane-Controlled Transdermal DDS Components
What is the purpose of the rate-controlling membrane?
controls the diffusion rate of drug from the reservoir into the skin – drug release control
Membrane-Controlled Transdermal DDS Components
What is the rate-controlling membrane typically composed of?
- poly(ethylene) (Nicoderm)
- ethylene-co-vinyl acetate (EVA) (Estraderm)
- EVA + other polymers
Membrane-Controlled Transdermal DDS Components
What is the purpose of the adhesive?
allows the patch to remain in place
- must be permeable to the drug and be biocompatible
Membrane-Controlled Transdermal DDS Components
What is the adhesive typically composed of?
- poly(acrylates)
- silicones (Duragesic)
- poly(isobutylene) (Transderm V)
Membrane-Controlled Transdermal DDS Components
What is the purpose of the release liner?
to prevent the adhesive from sticking to
packaging or unwanted sites prior to use
- is removed and discarded prior to application
- mmust be impermeable to the drug and release easily from adhesive
Membrane-Controlled Transdermal DDS Components
What is the release liner typically composed of?
polyester or polypropylene coated with fluoropolymer (non-stick)
Drug Release from Membrane Controlled Transdermal DDS
Fick’s Law of Diffusion
What are the major components of matrix (monolithic) transdermal DDS? (3)
- outer backing – impermeable metal/plastic laminate
- drug-loaded matrix
- two general designs with regards to the adhesive layer – may be a rim around the drug matrix or the matrix itself may be adhesive
What are the characteristics of matrix (monolithic) transdermal DDS? (3)
- no rate-controlling membrane – skin controls the rate of drug absorption, useful for drugs with a wide therapeutic index
- thinner and smaller than membrane-controlled devices
- release is not constant (zero order) but is controlled and predictable (first order)
What are some examples of matrix (monolithic) transdermal DDS?
- Nitrodur (nitroglycerin)
- Minitran (nitroglycerin)
- Climera (estradiol)
- Estradot (estradiol)
- Oxytrol (oxybutynin)
- Ortho Evra (norgertromin/ethinyl estradiol)
What are the disadvantages of transdermal DDS? (6)
- lack of dosing flexibility
- dosing fluctuations
- drug must have high biological activity
- only a few suitable drugs
- adhesion problems
- rate-controlling membrane technology is expensive
Would you recommend that a patient cut a transdermal patch to adjust the dose?
–
What is the stratum corneum?
primary barrier for absorption of drugs through the skin
- major limitation for types of drugs selected for TDD
Methods are needed that can overcome the barrier of the stratum corneum. What should they be able to do? (3)
- increase skin permeability reversibly
- provide an added driving force for transport (ie. better than what is being used currently)
- avoid damage to deeper, living tissue
What technologies have been developed?
- iontophoresis
- spray on
- microneedles
What is iontophoresis?
movement of drugs through the skin using an electrical current
- charged drugs are moved via electrophoresis
- weakly charged drugs or neutral drugs move by electroosmotic flow of water generated by the movement of positive ions (Na+)
- allows for change in the delivery rate by changing the current (may be patient-controlled)
What is iontophoresis limited by?
skin irritation and pain
What is iontophoresis currently used for?
to rapidly administer lidocaine
What are microneedles?
- size is small (300 μm) – they do not reach nerves in the dermis and are ‘painless’ (pressure feeling)
- single or arrays of microneedles – epidermis/dermis
- hollow microneedles deliver drugs from a reservoir
- solid microneedles are coated with the drug
What are microneedles most promising for?
vaccination – because they are often dose-sparing over IM injections
- no training required
- mass distribution
- painless
- patient administered
What are the type of microneedles? (4)
- solid MN
- coated MN
- dissolving MN
- hollow MN
What are solid microneedles?
coated with the drug
What are some applications of microneedles?
- injection (cosmetics) – botox, tattoos
- injection (biomedical) – vaccines, allergy tests, insulin, human GLP-1 analog for type 2 diabetes treatment
- extraction – continuous glucose monitoring, blood sampling, interstitial fluid extraction and analysis for therapeutic drug monitoring
What are the components of spray-on systems? (3)
- solution containing the drug
- volatile solvent
- chemical penetration enhancer
What do transdermal spray-ons do?
promote drug delivery via the complex interplay between solvent evaporation and drug–solvent penetration
What are the advantages of transdermal spray-ons?
- applied to a defined surface area
- cost-effective
- flexible dose administration
- less irritation
- aesthetically acceptable
What are the disadvantages of transdermal spray-ons?
- 50% of the drug remains on the surface
- drug transfer via skin contact
