Topical preparations Flashcards
Skin functions
The skin is an active barrier, regulates body temperature, mediates sensation, expresses emotion and identifies us.
Skin damages easily: mechanically, chemically, biologically and via radiation.
Applications of the skin
Manipulate barrier- infection, protection, emollient
Local treatment- anti-inflammatory, symptomatic relief
Systemic- transdermal drug delivery, NSAIDs, motion sickness, angina, hypertension
via skin, eyes, gums, rectum, vagina
Targets within the skin
Skin surface- protective layer, antibacterials/ anti-fungals
Stratum corneum- emollient, hyperkeratosis
Skin appendages- hyperhidrosis, acne, antibiotics, transfollicular absorption
Viable epidermis/ dermis- steroids, anti-inflammatories, antipruritics, anaesthetics
Systemic delivery
Factors affecting delivery
Skin age Skin condition Skin region- plantar, palmar, scrotal, scalp, arm, leg, trunk Skin metabolism Species (testing topical formulations)
Topical semi-solid formulation definition
Semi-solid preparations for cutaneous application are intended for local or transdermal delivery of active substances, or for their emollient or protective action.
Formulation of vehicles
Components: powders, liquids, semi-solids
Often need complex multi-phase systems to allow for a number of effects (usability, absorption, emollient action, symptomatic relief)
Vehicle itself must promote healing and not cause further damage
Ointments
Soft semi-solid preparations
Single phase base in which solids/ liquids may be dispersed
Emollient action without absorption through skin
Protective effect against environment
Intended to adhere to the skin and mucous membranes for localised delivery
Types: hydrophobic, water-emulsifying, hydrophilic
Ointment bases- hydrocarbons
Hard, soft and liquid paraffins
Most widely used
Form a greasy film on the skin, reducing moisture loss and improving hydration (including absorption)
Relatively inert, few incompatibilities
Soft paraffin often mixed with liquid and hard paraffin to make it easily spreadable with consistent rheological properties
Ointment bases- fats and fixed oils
Vegetable origin- peanut, sesame, olive, cotton seed, almond etc.
Mixtures of saturated and unsaturated fats
Can decompose on exposure to air, light and increased temperature (rancidity)
Rancidity increased by metallic impurities
Occlusive and sticky
Allergy is a concern with arachis (peanut) oil
Ointment bases- silicones
Water repellant
Used in barrier creams to protect against water soluble irritants
Ointment bases- absorption bases
Soak up water to form water-in-oil emulsions
Anhydrous vehicles composed of a hydrocarbon base and an emulsifier
Deposit a greasy, occlusive film (less suppression of trans-epidermal water loss than hydrocarbons)
Hydrates stratum corneum
Ointment bases- emulsifying bases
Anionic, cationic or non-ionic (o/w emulsions)
Contain surfactants therefore may help spreading
Mix with aqueous secretions and readily wash off skin (useful for scalp treatments)
Ointment bases- water soluble bases
Prepared from polyethylene glycols (high and low MW)
Suitable combinations provide an ointment-like consistency
Non-occlusive, do not stain clothing
Used with lignocaine but incompatible with many chemicals
Can be used to incorporate drugs dissolved in water
Preparing ointments
Insoluble ingredients must be finely powdered
Medicament incorporated into base by geometric dilution
Pastes
Ointments containing 20-60% powder dispersed in (soft paraffins, glycerol, emulsifying ointments)
Absorb noxious chemicals (ammonia from bacteria)
Localise drug action (reduce irritancy/ staining)
Less greasy than ointments
Sun-wind filters
Unsuitable for application to hairy or widespread areas
Creams
Creams are emulsions therefore they are inherently unstable systems
They are stabilised by the emulsifying agent
Anything which affects the emulsifying agent can alter the stability of the cream
Phases of creams
Creams are multiphase preparations consisting of a lipophilic phase, an aqueous phase and an emulsifier
Hydrophobic creams have a water-in-oil emulsifying system- low HLB. They are immiscible with water.
Hydrophilic creams have an oil-in-water emulsifying system- high HLB. They are miscible with water.
Emulsifying waxes and ointments
These form the basis of many o/w creams- the emulsifying wax contains the emulsifying agents, addition of the oily phase gives an emulsifying ointment, addition of water gives the cream
Emulsifying waxes and the corresponding emulsifying ointments are available to form the basis of anionic creams, cationic creams and nonionic creams
Emulsifiers
Mixtures of oil soluble alcohols and surfactants form stable, complex, condensed films at the o/w interface. The interfacial tension is reduced far lower than through use of either component alone.
Charge contributes to the emulsion stability via electrical repulsion. Non-ionic surfactants sterically retard colaescence through repulsion of hydrated ethylene oxide chains.
Stabilising emulsions
The adsorption of a surfactant at the globule interface lowers the o/w interfacial tension enhancing stability. Whether or not the surfactant will stabilise the emulsion will depend on the type of film (barrier) formed at the interface.
Hydrophilic creams (oil in water creams)
Non-occlusive/ slightly occlusive
Also known as vanishing creams- thin oily film
Promote percutaneous absorption via concentration gradient
Propylene glycol added to reduce drug precipitation
Preservation of creams
Contain water therefore can support the growth of micro-organisms
Preservative required
Good preparation technique limits contamination
Purified water (freshly boiled and cooled)
Expiry date
Other non-therapeutic ingredients of creams
Lipid vehicle Co-solvent to help drug dissolve w/o emulsifier o/w emulsifier Buffer for drug stability Humectant to minimise water loss from the formulation Antioxidant Penetration enhancer Moisturiser and lubricant to improve cosmetic properties
Preparing creams
Heat hydrophobic and hydrophilic ingredients separately
Mix at same temperature
Put energy into system
Adjust weight
Medicament dissolved in appropriate phase or added to the prepared cream by levigation
Gels
Transparent or translucent semi-solid or solid preparations made with a suitable gelling agent
Usually non-greasy, high water content, easy to remove from container, good release properties
Continuous 3D structure providing solid-like properties
Types of gels
Flocculated lyophobic sols e.g. aluminium hydroxide gel
Floc of clays e.g. bentonite
Lyophilic gels- network formed by entanglement or attraction between molecules (H-bonds, VdW forces) e.g. agar, increase in temperature can break bonds and liquefy gel i.e. thermal gels
Irreversible gels e.g. silica gels used as a dessicant due to water adsorbing properties
Rheology
Semi-solid topicals show complex rheological properties
Prone to structural breakdown, thixotropy and viscoelasticity
