Topical drug delivery Flashcards
What is Topical drug delivery?
Delivery of drugs at the surface or to the skin
This is to treat skin conditions
What is Transdermal drug delivery?
Delivery of drugs to the bloodstream through the skin
Types of drugs administered to the skin for topical delivery
CLAAAAP
Anti-inflammatory drugs (corticosteroids) - Eczema, skin allergy, insect bites…
Local anaesthetics (lidocaine, benzocaine)
Antiseptics – wounds, leg ulcers
Anti-infectious agents (antibacterial, antifungal, antiviral, parasiticidal)
Anti-acne (benzoyl peroxide)
Psoriasis drugs (dithranol, vitamin D analogues, retinoids)
Cytostatics – skin cancer
What are the advantages of topical drug delivery?
Easy + Painless delivery
High patient compliance
Avoid FPM in the liver
Increased efficacy
Decreased side effects
Wha are the disadvantages of topical drug delivery?
FLOPS
Frequent allergies
Only a few drugs have suitable properties for drug delivery
Prescence of enzymes in the skin
Low drug penetration in skin
Skin is a very efficient barrier
Describe the structure of the skin
What is the function of the skin?
Effective barrier against penetration of chemicals/microorganisms - That includes drugs!
Control of body hydration and temperature
Protection against UV radiation
Mechanical barrier
What is the main barrier for drug permeation?
Stratum Corneum
Describe the Stratum Corneum
10-15 layers of corneocytes - (dead cells derived from keratinocytes)
Tightly compacted cell layers
Polygonal, elongated, flat cells
Cells mostly contain keratin
Embedded in lipid bilayers (ceramides, fatty acids, cholesterol but no phospholipids)
« brick and mortar » model
Name the penetration pathways through the Stratum Corneum
Transappendageal
Transcellular
Intercellular
What is the Transappendageal pathway?
Transports substances via sweat glands and the hair follicles with their associated sebaceous glands
This route is considered negligible because of its relatively small surface area (0.1%).
What is the Transcellular pathway?
Polar route for hydrophilic molecules
Unfavourable (drugs need to partition into lipid bilayers between the cells)
What is the Intercellular pathway?
Less polar route for hydrophobic molecules
Favourable (continuous pathway)
What are the main factors that affect drug permeation?
Biological factors
Drug properties
Vehicle properties
What are the Biological factors?
Skin hydration - Increases drug penetration (both for hydrophilic and lipophilic molecules)
Age - Decreased skin moisture content with age
Body site - Thickest SC on the palms of the hands and sole of the feet, thinnest on the lips and eyelids
- Order of permeability: Genitals > head and neck > trunk > arm > leg
Pathological disorders - Damaged stratum corneum if infection, eruptions, tumours
What are the drug properties?
Molecular weight - Poor penetration if >500 Da
Partition coefficient between vehicle and skin - Log P (octanol/water) between 1 and 3 - Drug with Log P > 3 might accumulate in the stratum corneum
pKa - Drug must be neutral at the pH of the skin (-5)
Concentration in vehicle - Diffusion into the skin depends on the concentration gradient
How can we modify drug physicochemistry for increase drug permeation into the skin?
Prodrugs
Attach lipophilic moieties to increase partitioning into stratum corneum
Esters cleaved by esterases to release parent molecule
Dramatic increase in skin permeation
What are the drawbacks of using prodrugs?
They are new chemical entities - toxicity tests + clinical trials must be performed before approval
What should be the Vehicle properties?
Occlusion - ointment + w/o cream prevents evaporation from the skin
- increases hydration + drug permeation
Permeation enhancers used in many components
- chemical agents which decrease the barrier properties of the stratum corneum w/out damaging underlying cells
Examples of prodrugs for topical delivery
Betamethasone-17-valerate
Hydrocortisone Butyrate (Potent)
Types of formulations for topical drug delivery
Liquid formulations - lotions
Semi-solid formulations
Examples of Liquid formulations
Solutions (cetrimide, scalp lotions)
Emulsions (hydrocortisone)
Examples of Semi-solid solutions
Ointments
Creams
Gels
What are Ointments?
Greasy preparations
Mixture of waxes, fats + oils
One single hydrophobic phase
What are Creams?
Semi-solid emulsions - w/o or o/w
2 liquid phases - internal phase dispersed as globules in external phase
What are Gels?
Continuous liquid phase thickened by polymers
Mechanism of action of permeation enhancers
Modification of keratin conformation - swelling - increased hydration
Disruption of the lipid bilayers = increased permeability
Alteration of solvent properties of stratum corneum = increased partitioning
What helps topical drug delivery?
Vehicle - increase water content - decrease barrier properties of stratum corneum
Examples of permeation enhancers
Solvents (dimethylsulfoxide, ethanol, propylene glycol)
Fatty acids, surfactants
Urea
Terpenes (essential oils)
