Transdermal And Topical Drug Delivery Flashcards
What are there disadvantages of transdermal drug delivery?
Only suitable for drug molecules with specific physicochemical properties that do not harm the skin. (Drugs must be potent but non irritant)
Intra and inter variabiltiy associated with the permeability of intact and diseased human skin.
Dermal metabolism
Skin irritation and sensitisation
Technical difficulties in adhesion
Skin is a strong barrier for drug absorption
What are the advantages of transdermal drug delivery?
Avoids chemically hostile GI environment Avoids first pass metabolism Reduced side effects Reduced drug dosing (controlled release) Easy to administer / painless Better patient adherence Direct targeting of tissue Rapid termination
What are the main functions of the skin?
Protection against external stimuli Heat regulation Water resistance Control of evaporation Storage and synthesis
What are the three main layers of the skin?
Epidermis, dermis, hypodermis
What are the components of the epidermis?
Stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, stratum basale
What are the components of the dermis?
Sebaceous gland, sweat duct, sweat gland, blood vessels,
Fibrous proteins, glycosaminoglycans, lymphatic vessels, hair follicles
What are the components of the hypodermis?
Lymphatic vessels, fat globules
What are the components of the stratum corneum?
Cornified cell envelope which surrounds each corneocyte. (Like an oval)
Cormeodesmosome which connects corneocytes together.
Natural moisturising factor inside the corneocytes
Extracellular lipid (kind of like background)
Stratum granulosum which supports the corneocytes
What is the stratum corneum?
The uppermost layer of the skin.
Main barrier to drug transport as it is very dense
Consists of terminally differentiated keratinocytes (now known as corneocytes) 10-15 layers
Where are corneocytes embedded?
Into the lipid rich bilayer called mortar, in the stratum corneum
What is the function of corneocytes?
They protect the skin from physical and chemical damage
What are the two main parts of the epidermis?
Viable epidermis (consists of live cells) And inviable epidermis (consists of dead cells)
What makes up the viable epidermis?
Stratum basale
Stratum spinosum
Stratum granulosum
Stratum lucidum
What to makes up the inviable epidermis?
Stratum corneum
What is the dermis?
3-5mm thick
Functions to cushion, stretch and strength
Provides nutritional support to the epidermis
Also involved in metabolism/synthesis
What are the permeation pathways for a transdermally delivered drug?
Drug is released from the device, travels into stratum corneum, and partitions and diffuses into the subcutanesous layer.
It then diffuses into the viable epidermis which is a metabolic site, here some of the drug molecules will reach a receptor, while others will continue to partition into the dermis.
The dermis is another metabolic site, drugs here will reach another receptor and will also be removed systemically and lymphatically.
Drugs removed systemically will then partition and depot into fat tissue
What are the different permeation pathways?
Intracellular route
Transcellular route
Transappendageal route
What is the intracellular route?
Between the cells
What is the Transcellular route?
Through the cells
What is the appendageal route?
About 0.1% of drugs.
Aka stunt route.
This is through the hair follicles and sweat ducts
What is passive diffusion?
The movement of drug into the deeper layers of skin following random molecular motion.
The transfer rate of the diffusion drug is proportional to the concentration gradient.
What is fick’s first law of diffusion?
Flux is proportional to the diffusion coefficient, initial concentration, partition coefficient, and is inversely proportional to the thickness of the membrane or total path length.
What are the he ideal drug properties for transdermal drug delivery?
Low molecular weight (<200 °C)
Must be highly potent (affinity vs. Conc.)
Must not be irritant to the skin
What factors affect percutaneous absoprtion?
Three main classes:
Physicochemical factors
Biological factors
Formulation factors
What are the physicochemical factors that affect percutaneous absoprtion?
Partition coefficient: log p and K
Solubility/drug concentration
Molecular size and weight
Diffusion coefficient
What are the biological factors which affect percutaneous drug absorption?
Area of application
Age, sex, race of patient
Condition of skin
How do conditions of the skin affect percutaneous drug absorption?
Patients with dermatitis have better absorption than people with psoriasis
Those with dermatitis with thicker skin means drug permeation goes down
Level of hydration is also important.
As is the level of convection
How do formulation factors deck percutaneous drug absoprtion?
We have a range of strategies which can be optimised to achieve better drug delivery into the blood.
-Drug vehicle interaction
Pro drug: we utilise the enzymes in the skin to metabolise it to its active form.
Eutectic mixtures: This is where you have a mixture of compounds where you get a lower melting point
Novel vehicles
Liposomal based delivery systems
Nano particles: e.g. Powdered drug and use a gun to shoot it into the skin,
Penetration enhances, these can be chemical or physical.
Iontophoresis relies on weak current but this is only really used for water soluble drugs.
Electroportion, where a strong current which can be repeated, but this is mostly for big molecules like DNA.
What are the main components of a transdermal patch?
Impermeable backing Drug in adhesive Drug in reservoir Rate controlling membrane Pressure sensitive adhesive Removable release liner
What are the two types of transdermal patches?
Drug in adherence
Multilaminate
Liquid reservoir
Polymer matrix
What are the components of a Drug in adhesive patch?
Impermeable backing
Drug in adhesive matrix
Remove able release liner
What are the components of a multilaminate patch?
Impermeable backing
Drug in adhesive matrix
Rate controlling membrane
Removable release liner
What are the components of a liquid reservoir patch.,
Impermeable membrane Liquid reservoir Rare controlling membrane Adhesive matrix Removable release liner
What are the components of a polymer matrix patch?
Impermeable backing,
liquid reservoir,
adhesive matrix,
removable release liner
What is an example of multi laminate transdermal patch?
Catapress
Consists of backing layer of pigmented polyester film
Drug is clonidine,
The reservoir contains clonidine, mineral oil, polyisobutylene and colloidal silicon dioxide.
Control membrane with microporous polypropylene membrane
Adhesive with clonidine, Mindel oil, polyisobutylene and colloidal silicon dioxide..
The release rate is 4.32+/- 1.68μg per sq. cm per hour for 7 days
What are microneedles?
Transdermal patch like devices fabricated from silicone, glass, metal, titanium, polymer and sugar.
Consists of arrays of vertical projections on their surface
Designed to create microscopic pores in the skin
What are chemical penetration enhancers?
Any substances that can modify the arrive properties of the subcutaneous tissue to enhance drug permeation and absorption through the skin.
What are the ideal characteristics of a permeation enhancer?
Reversible reduce barrier resistance of the SC without damaging viable cells
Be non toxic, non irritating, and non allergenic
Work rapidly, the activity and duration of effect should be both predictable and reproducible
Have no pharmacological activity within the body
Be cosmetically acceptable with an appropriate skin feel.
What is the mechanism of chemical enhancement?
Substance essentially extracts phospholipids from the intercellular bilayer, thus disrupting their structure. This results in fluidisation which enables substances to penetrate the skin better
What are commonly used chemical penetration enhancers?
Water Sulfoxide and similar chemicals e.g. DMSO Azo a Pyrrolidons Fatty acids Alcohols Surfactants Urea Essential oils Terpens, Terpenoids
What is the most ideal penetration enhancer?
Water.
In general,can increase in hydration can increase the permeability of both hydrophilic and lipophilic permeant,
Think of occlusion medicaments and w/o emulsions
What is the limitation of using water as a penetration enhner?
Cannot be used for poorly water soluble permeant
