Topical Preparations Flashcards
Describe topical
Administered on tissue surface
Local condition
Site administration is site of therapeutic action
Commonly skin
Why do it minimise systemic?
To minimise side effects
How is it different to transdermal?
Administered on skin surface
Act at remote site away from site administration
Requires systemic drug absorption
What are advantages?
Avoid GI + 1st-pass Non-invasive Patient compliance Better drug targeting = minimal systemic side effects Easy dose withdrawal
What are disadvantages?
Low skin permeability
Skin irritation
Difficult to determine dose
What is problem with low skin permeability?
Only small section of drugs deliverable + uptake slow
Describe ointment
Drug dissolved or dispersed in greasy base
Occlusive
What are disadvantages of ointment?
Difficult to spread
Patient acceptability could be low
Why is ointment occlusive?
Promotes skin hydration by minimising trans epidermal H2O loss
Describe cream
Semi-solid emulsion
Multiphase dispersion of O/W or W/O
Longer residence time than lotion
What are advantages of cream?
Mixable with skin secretions, easily washable
Excellent patient acceptability
Less greasy than ointment
Describe gel
Semi-solid, often clear
Polymer network interpenetrated by liquid
Mostly aq
Drug dissolved in liquid component
What disadvantage of gel?
May form occlusive film on skin when dried
Describe lotion
H2O based = non-occlusive
Solution, suspension or emulsion
What is lotion used for?
Cleaning or disinfection
What are advantages of lotion?
Highly spreadable
Suitable for hairy skin
Why is it good it is highly spreadable?
Ideal for covering large area thinly
What is the problem of lotion?
Short residence time
How to fix short residence time of lotion?
Increase viscosity
Describe foam
Dispersion of gas within liquid
Drug dissolved in liquid phase
What is foam available in?
Pressurised cans
How does foam work?
Generated during use + stable only momentarily
Describe spray
Aerosol = dispersion of liquid droplets in gas
Fine mist generated using propellant in pressurised can
What is advantage of spray?
Administration without direct skin contact
Rapid + even coverage of large SA
Describe patch
Similar to trans dermal BUT for topical delivery
Solid dosage form containing drug on adhesive film
What are advantages of patch?
Discrete dosage unit = enables accurate dosage
Provides occlusion, dose retention + protection of formulation
What are the dermal drug transport mechanism?
Partitioning
Diffusion
Describe partitioning
From one medium into another, solubility-driven
Describe diffusion
Within same medium, down conc gradient
What is skin permeability?
Function of partitioning coefficient + diffusion coefficient
How do you calculate permeability coefficient?
Kp = KD/ h
Kp = permeability coefficient K = partition coefficient D = diffusion coefficient h = Diffusion pathway length
What is the transcellular route?
Straight through corneocyte = hydrophilic drug
What is paracellular route?
Around corneocyte through lipids = lipophilic drug
What is the shunt pathway?
Through hair follicles + sebaceous glands
Why is the shunt pathway important?
For innovative drug delivery strategies
Why is the shunt pathway traditionally regarded as negligible?
Small skin area
What factors affect dermal drug transport?
Drug properties
Lipophilicity (logP 1-4) Molecular weight (<5000)
What factors affect dermal drug transport?
Anatomical site
Barrier thickness
Hair follicle density
What factors that affect dermal drug absorption?
Age
Disease
Why is age a factor that affect dermal drug absorption?
Thickness, hydration, lipid content + microvascular clearance decline with age
Corneocytes enlarge with age
Why is disease a factor that affect dermal drug absorption?
Broken skin = highly permeable Scaly skin (peeling) = impaired permeability barrier BUT also dehydrated = reduce permeability Thick skin = reduced permeability = increased diffusion pathway length
What do you asses with in vivo dermal drug transport?
Ethical considerations
Clinical support
Suitability of animal method
What do you asses with in vitro dermal drug transport?
Ethical considerations
Suitability of skin model
How is drug lost from applied dose?
Remaining dose on administration site
Describe microdialysis
Semi-permeable tube inserted surgically below skin
Permeated drug collected in perfusate
Describe tape stripping
Stratum corneum progressively removed by adhesive tape
Drug assayed relative to protein content of strip
What must be assumed in tape stripping?
Each strip removes materials from single cellular layer
What is a problem with tape stripping?
Tape constituents may contaminate sample
What is the problem with microdialysis?
Invasive
What are the three types of diffusion cells?
Franz-type vertical
Side-by-side
Flow-through
Describe what happens in diffusion cell
Skin sandwiched between donor + receptor channels
Stratum corneum facing donor chamber
Drug formulations administered into donor chamber
Receptor chamber filled with receptor buffer
Drug can only pass through skin to receptor chamber
Drug sampled from receptor + assayed
What is the mass balance?
Diffusion cell
Drug recovered from donor chamber + drug extracted from skin + drug assayed in donor receptor + 100% dose
