Topicals Flashcards
What does topical mean?
Applied to any external body surface for a localised effect e.g. eye, nasal mucosa, skin, scalp
Why do we give treatment locally to the skin?
- To enhance barrier function of the skin
- Targeted delivery to specific layers of the skin e.g. fungal infections are in the outermost part of skin but for eczema need to deliver drugs deeper into the skin
- Better to give a topical formulation to treat the skin as fewer side effects compared with oral delivery of drugs
How do formulations improve skin’s barrier function?
- Sunscreens protect against UV radiation
- Antibiotics for abrasions protect against infection
- Emollients improve dry skin conditions
- Moisturisers protect against drying atmospheric conditions
- Barrier creams prevent exposure of skin to harsh chemicals
Skin Structure - 3 main layers
Stratum corneum is outer
layer of epidermis
Skin cells begin life in
the stratum basale layer
of the epidermis
Blood vessels are
present in the dermis
but not the epidermis
Sweat glands, hair follicles
and sebaceous glands
originate in the dermis.
The subcutaneous layer
is fatty tissue that acts as
“cushion” for the skin
What topical dosage form should you select for application to the skin?
- Skin surface = on the skin
- Stratum corneum = in the skin
- Viable epidermis = deeper in the skin
- Dermis = underneath the epidermis
- Do you need to treat the skin appendages = hair, sweat glands, sebaceous glands, nails
Target above the stratum corneum (SC), to the SC or below SC
- Above or on the skin – easier target. This is where we apply sunscreens, insect repellents
- Below the skin surface or into the skin – more difficult target
- Treat the stratum corneum if for example fungal infections present
- But if treating epidermis or dermis the formulation must allow drug to cross stratum corneum = percutaneous absorption of drugs
What type of topical dosage forms are currently available?
Semisolids = halfway between solid and liquid and include: Ointments, pastes, creams, lotions, jellies, gels, liniments, collodions, plasters
Topical solutions
Soaps/shampoos
Tinctures
Powders
Aerosols/Foams
Topical patches
Occlusive VS non-occlusive topical formulations
- Occlusive means that the formulation prevents water movement out of the body. So an occlusive preparation increases skin hydration and moisture content by “locking in” the water present in the body
- Good for dry skin but bad for infected skin
- Enhances skin barrier as forms a “shield” on skin
- Good penetration of drugs through the skin
What are ointments?
Semisolid preparations intended for external application to the skin or mucous membranes
2 types of ointments for the skin
- Composed of hydrocarbons (not water soluble)
- Water soluble ointments
Types of soft paraffin hydrocarbons
- Yellow petrolatum (Petroleum Jelly) Vaseline
- White petrolatum (white petroleum jelly) has been bleached to remove yellow colour
What other types of oils are found in hydrocarbon ointments?
Vegetable oils from plant sources e.g. peanut, castor, olive, coconut. These oils may be thickened with a high melting point material such as cetosteary alcohol
Synthetic oils such as silicone oils (Dimethicone BP) used as water repellents.
Isopropyl myristate is semisynthetic and similar to the vegetable oils in its properties and uses.
Properties of hydrocarbon ointments
- Occlusive
- Emollient
- Hydrate skin due to moisture accumulation
- Skin hydration keeps skin supple
- Difficult to remove, just water does not work
- Greasy
- Good if drug not stable in water
Water soluble ointments
These ointments are water soluble or washable
Examples include macrogol ointment (polyethylene glycol ointment). This is a polymer so we can control the length of the polymer to produce whatever type of preparation we want.
The longer the chain length of the polymer the higher the melting point of the ointment.
Can mix short and long chain polymers to produce different ointments with different melting points
Examples of products with water soluble ointment bases
Bactroban ointment contains mupirocin - used for treatment of skin conditions
Iodosorb ointment consists of a form of ionine in a macrogol ointment base, used for wound management
Properties of water soluble ointments
- Water soluble
- Washable
- Non greasy
- Non-occlusive or not as occlusive as hydrocarbon ointments so they do not lock water in as well as hydrocarbon ointments
Pastes
We can have 20-50% of solid materials
Stiffer than ointments
Good protective barrier - water impermeable
Prevent dehydration e.g. pastes are used to prevent windburn
Pastes are used to prevent nappy rash - absorb ammonia from break down of urine
Creams
Two phases, oil phase and a water phase
Either o/w or w/o
Need emulsifiers to keep the droplets suspended
Need a preservative to stop contamination because water is present in creams
Why are creams popular for topical application?
- Good delivery system for many drugs
- Good patient acceptability
- Spread easily
- Not as occlusive as ointments
- For o/w creams, water evaporates to leave a thin “film” on the skin
How are emulsifiers used to make creams?
Select emulsifier depending on whether a w/o cream or a o/w cream is needed
w/o emulsifiers include wool fat (lanolin) which is a pale, yellow sticky material composed of fatty acid esters of cholesterol and other sterols
It is similar to human sebum but can cause sensitisation in some patients
Emulsifiers in w/o creams
- Wool alcohols
- Richer in cholesterol and lanesterol and freer of impurities than wool fat
- Hydrous wool fat is 7 parts wool fat, 3 parts water and is softer than wool fat or wool alcohols
- Beeswax is a traditional w/o emulsifier composed of fatty acid esters and long chain alcohols
Examples of w/o creams
Drapolene cream for nappy rash
Boots chilblain cream
Emulsifiers in o/w creams
- Emulsifying waxes - 3 types:
Each one has 2 ingredients - cetostearyl alcohol (CSA) and a surface active agent
1. Emulsifying wax BP contains sodium lauryl sulphate and CSA (1:9)
2. Cetrimide emulsifying wax BPC contains cetrimide and CSA (1:9)
3. Cetomacrogol emulsifying wax BPC contains cetomacrogol 1000 and CSA (8:2)
Miscellaneous emulsifiers
- Calcium soaps are produced by mixing a fatty acid with lime water (calcium hydroxide solution) to form a soap. They are used to form w/o emulsions
- Synthetic surface active agents can also be used. Low HLB materials produce w/o emulsions and higher HLB materials give o/w emulsions
- HLB – hydrophilic lipophilic balance
Examples of o/w creams
Aqueous cream
Hydrocortisone cream
Lotions
Liquid
Contains insoluble solids which need to be suspended
Low viscosity so lotions spread very easily and they are easy to apply
Dry on skin quickly after application
Calamine lotion
Main components
- Calamine, zinc oxide (solids)
- Glycerol (helps to keep skin moisturised)
- Phenol – antibacterial agent
- Bentonite (a clay which helps to keep the solids suspended in the lotion)
- Water
Pink colour of calamine lotion comes from iron oxide in calamine
Liniments
- A lotion with oils
- Similar viscosity to lotions but rubbed in with pressure
- May contain methyl salicylate or other materials which act to relieve pain and stiffness
Powders
- Applied to the skin for a surface effect such as drying or lubricating or for an antibacterial or antifungal action
- Made of fine particle size powders combined with any medicaments
e.g. Daktarin powder
Tinctures / paints
- Alcohol based solutions
e.g. iodine tincture
Used for pre-op skin disinfection
Gels
- Solid or semisolid preparations
- Require a gelling agent
- Gelling agents used can be natural or synthetic
- Examples of natural gelling agents are tragacanth, pectin, alginate
- Examples of synthetic gelling agents include synthetic polymers e.g Carbomer, Cellulose
- Gels are usually transparent or translucent
Gelling agents - how do they work?
- The gelling agent forms a cross-linked network in liquid
- So gels are a dispersion of liquid within a solid where the solid is the continuous phase and the liquid is the disperse phase
- Hydrogels are based on water and are formed by a hydrophilic polymer swelling in water
Carbomer gels
- Produce gels with few stability problems
- Are carboxy vinyl polymers which form a low viscosity dispersion with an acid pH in water
- When the dispersion is neutralized by the addition of alkali, a gel is formed
- Water soluble alkali - Triethanolamine
- Alcohol soluble amine - Diisopropranolamine
Examples of topical gels
Ibugel
Ibuprofen
IMS
- Carbomer
Propylene glycol
Preservative
- Water
Isotrexin gel
- Isotretinoin and erythromycin
- Hydroxypropyl cellulose
- Ethanol
- Preservative
Topical patches
- Hydrogel with a backing layer
- Very popular in Asia but not used in the West until early 1990’s
Example - Lidocaine to treat
Postherpetic
neuralgia
Collodions
Sticky liquid which dries to a film
Used as a skin protectant, applied to the skin to close small wounds, abrasions, and cuts, to hold surgical dressings in place, and to keep medications in contact with the skin
e.g. salactol to treat warts
Where do sunscreens have to stay?
Sunscreens must stay largely on skin surface so ointments too occlusive. Gels, sprays, creams and lotions are preferred.
Where do fungal infections reside?
Fungal infections reside in the stratum corneum so need to deposit the antifungal drug in the outer layers of skin not in deeper layers, so again, ointment not appropriate
Where in the skin is inflamed skin associated with?
Inflamed skin often associated with problems in skin barrier so ointments good
Transdermal delivery VS topical delivery
- Topical delivery does not aim to get the drug into the bloodstream
- Transdermal delivery does aim to get the drug into the bloodstream
- Transdermal delivery avoids the problems associated with oral delivery (break down in the stomach and gut)
- Associated with better patient compliance
Transdermal patches
Adhesive patch placed on the skin to deliver medicine all the way through the skin and into the bloodstream
Drugs administered via patch
Fentanyl
Nicotine
Nitroglycerine
Estradiol
Ethinyl Estradiol/Norelgestromin
Testosterone
Examples of transdermal patches
Transiderm-Nitro (Nitroglycerine)
Nicotinell (Nicotine)
Durogesic (Fentanyl)
Estraderm (estradiol)
Evra (Ethinyl estradiol/Norelgestromin)
Examples of transdermal gels
Testogel
Oestrogel
Limitations of transdermal patches or gels
- Skin is good barrier and large amounts of drug cannot permeate.
- Maximum daily dose ~ mg per day.
- Maximum attainable flux across the skin therefore important.
- Influenced by drug properties
