Topical preperations Matt Ivory Flashcards
How can the skin be damaged?
Mechanically
Chemically
Biologically
Via radiation
Whta are the different skin applications?
- Manipulate the barrier - protection and treat infection
- Local treatment - anti-inflammatory, Sympotmatic relief
- Systematic - Transdermal drug delivery
NSAIDs - IBUGEL, motion sikness, angina
WHat are the different layers of skin that can act as drug targets?
1) Skin surface
2) Stratum Corneum
3) Skin appendages
4) Viable epidermis/dermis
5) systemic delivery
How does the skin surface act as a drug target?
Barrier cream will sit on top of the skin as a protective skin layer.
How does the stratum corneum act as a drug target?
Drug is delivered into the shallow stratum coreum affecting cells deeper in the skin e.g. keratinocytes
How does the SKin appendages act as drug target?
Affects the things attached underneath the skin e.g. hair follicles and sweat glands. This is shunt delivery (through a small passage)
e.g. Acne medication
How does the vaible epidermis/dermis act as a drug target?
Deliver the drug underneath the skin surface but not systemic e.g. steroids, and anti-pruritic drugs.
How does systemic delivery happen via the skin?
The drug is delivered beond the skin layers and into the blood e.g. nicottine patches.
What are the factors affecting delivery?
Skin age - older gets less elastic
Skin condition - non-healthy skin is comprimised
Region - some regions of skin are thicker or thinner than others, hairy or not etc
Skin metabolism - enzymes that break down active ingregients
Species.
What is a licenced medicine?
A medicine rigorously tested for quality, saftey and efficacy. They’re made in very large batches and is the cheapest option
What are special medicines?
These are made by manufacturer at request of pharmacy or doctor only. They are tested for quality only. Made in much smaller bacthes and are more expensive.
WHat are extemporaneously prepared medicines?
These have NO EVIDENCE OR ANY TESTING FOR SAFTEY OR QUALITY. Involves the mixing of two medicines in the pharmacy itself. SHoulnot be used unless completely neccessary. VERY expensive.
What is the purpose of Semi-solid preparations as topical preparations?
Semi-solids for cutaneous application are intended for local or transdermal delivery of active substances, or for their emollient or protective action.
What do we know about the formulation of a semi-solid formulation:
Often needs a complex multi-phase system to allow for number of effects- usability, absorption, sympomatic relief, emollient action etc.
Any vehicle added as an exipient must have a pharmacological benefit or not cause further damage.
The whole formulation must be compatible with patient
What are the different types of semi-solid preparations?
Ointments, pastes, gels, creams etc
OINTMENTS:
soft, semi-solid preperation.
Very basic
Single-phase base which solids or liquids may be dispersed
Emollient action:
Too oily to be absorbed throught he skin, so is a BARRIER cream to prevent things getting in, and also some prevent water loss
WHat ar ethe types of Ointments?
Hydrophobic (occlusive) - very oily to prevent water loss e.g. calamine lotion Water emulsifying (occlusive) e.g. wool alcohol ointment Hydrophilic (non-occlussive) less oily, doesn't prevent water loss e.g. Macrogol BP
If the skin isn’t dehydrated, what emollient is likely to be used?
Macrogol BP - non-occlusive doesnt prevent water loss.
What are the different types of ointment bases available?
Hydrocarbons Fats and fixed oils Silicones Absorption bases Emulsifying bases Water-soluble bases
What are hydrocarbons:
hard, soft and liquid PARAFFINS
These are the most widely used.
They form a greasy film on the skin reducing moisture loss and improving hydration.
Stable and relatively inert
WHat is the caustion with Hydrocarbons?
Paraffin is a Fire Hazard- don’t be near open flame with ointment on skin.
What are FAts and Fixed oils?
Natural Sources, Vegetable origin, Mixture of saturated and unsaturated fats
Not as stable as hydrocarbons.
These are occlusive and sticky
What are the issues with Fats and fixed oils?
Natural sources therefore batch variability.
Vegtable origin - issues with peanut allergies
Not as stable as hydrocarbons therefore can decompose on exposure to air, light and increased temp. Exposure to these will cause rancidity.
What are silicone bases?
These are water repellant - hydrophobic therefore occlusive. Used in barrier creams against water-soluble irritants.
What are adsorption bases?
These soak up water to form w/o emulsions, are occlusive but not as strong as hydrocarbons therefore some water can leave the skin, while also drawing water into itself to hydrate the stratum corneum.
What Are emulsifying bases?
Anionic, cationic, nonionic o/w emulsions.
Contain surfactants to help spreading by lowering the surface tension between liquid and solid.
These mix well with water and are therefore useful soap substitutes.
What are water soluble bases?
These are prepared from Polyethylene Glycols.
Suitable combinations provide ointment-like consistensy,
non-occlusive so water can leave the skin.
Used often with lignocaine, but incompatible with many chemicals.
Useful to incorporate drugs dissolved in water.
With the water soluble bases, how does the MW of the base affect the formulation?
High MW polythylene Glycol will be MORE viscous
Low MW polythylene Glycol will be LESS viscous
Depends on chain-length and tangling.
What is the first step in preparing ointments if the ingredients are INSOLUBLE?
The insoluble ingredients must be finely ground to a powder consistensy and then incorporated into the base by geometric dilution.
What are pastes?
These are very simple formulations.
Made using an ointment, add powder, and disperse. e.g. soft paraffin, glycerol, Magnesium sulphate BP.
How do pastes work?
They adsorb noxious chemicals e.g. ammonia from bacteria
They have a localised drug action normally to reduce irritation.
They are less oily, but thicker than ointments, and feel more gritty.
Where are pastes not suitable to be used on the skin?
Not suitable for hairy areas or wide spread areas as too thick.
What are Creams?
These are more complex formulations.
They are emulsions, therefore they are multi-phase and therefore inherently are UNSTABLE systems.
How are ceams stabilised?
They are stabilised with Emulsifying agents
What are the phases in a creaM?
Multi-phase
- Lipophilic phase
- Aqueous phase
- Emulsifier (emulsifying agent)
What is HLB and how does it afect creams?
HLB - hydrophile-lipophile balance is very important as it tells us the type of cream it is i.e. w/o or o/w
What is a LOW HLB cream?
This is a Hydrophobic cream - w/o system that is imiscible with water. The continuous phase is water
What is a HIGH HLB cream?
This is a hydrophilic cream - an o/w system. Water is the continuous phase. it is miscible with water.
Why does coalesence happen?
To try to minimize the interfacial area, decreaing the free energy and making the system more stable. But we don’t want coalesence to happen.
What is an Emulsiying wax used in creams?
This is the basis of many o/w creams. The emulsifying wax contains an emulsifying agent. It is added to oil, to form the emulsifying ointment, which is then added to water to form the cream.
What emulsifier is used for Anionic creams?
Sodium lauryl sulphate
What emulsifier is used for Cationic Creams?
Cetrimide
What emulsifier is used for nonionic creams?
Cetomagrogol
What is the other component often added to creams and why?
Cetostearyl alcohol: Oil-soluble stabilizer, surfactant, viscosity-increasing agent, added to most creams.
How is the interfactial tnesion reduced in most o/w creams
Using oil-soluble alcohol and surfactants together at the interface of many o/w creams.
What is in Emulsifying wax?
oil-sol component: cetostearyl alcohol
water-sol component: sodium lauryl sulphate
What is in Cetrimide emulsifying wax?
oil-sol component: Cetostearyl alchohol
water-sol component: cetrimide
What is cetomacrogol emulsifying wax?
oil-sol component: cetostearyl alcohol
water-sol component: cetomacrogol.
How des charge affect the emulsion stability?
Via electrical repulsion.
What is in Aqueous Cream BP?
- Emulsifying wax: Cetostearyl alcohol and sodium lauryl sulphate
- Emulsifying ointment: White soft paraffin and liquid paraffin
- purified water FBC
What is interfacial tnesion?
The elastic tendance of a fluid surface which makes it aqquire the least surface tension possible.
The lower the surface tension, the more stable the cream.
How is the surface tension decreased?
The adsorption of surfactants at the globule interface will lower the surface tension, making it more stable.
Oil in water creams: is also known as the
Vanishing cream as water evaporates from te surface, leaving the oily phase as a thin film behind.
What is often added to reduce drug precipitation?
Propylene glycol
Give an example of an o/w cream
Aqueous cream BP (anionic)
What are hydrophobic creams?
They are primarily w/o cerams although some are o/w. They have a LOW HLB.
What are the incompatibilities of drugs and emulsifiers?
Anionic drugs are incompatible with cationic emulsifiers
Cationic drugs are incompatible with anionic emulsifiers.
Charges must be the same so that the molecules repell each other to prevent coalesence in an effort to reduce surface tension.
How do non-ionic emulsifiers work?
They work via hydrogen bond formation, and can be used with anionic and cationic drugs.
They can be hydrophilic or lipophilic depending on HLB
They have large, bulky heads, sterically hindering molecules from coming together.
What are the issues with non-ionic emulsifiers?
There are some issues with hydrogen bonding as they are very sensitive to temperature changes
What drugs are non-ionic emulsifiers incompatible with?
Phenolic drugs
Can non-ionic emulsifiers be used along with charged emulsifiers and why?
They can be used along cationic or anionic (depending on the drug) to increase stability.
WHy do creams need to be preserved?
need to be preserved as they contain water so susceptible to microbial growth.
They are also multi-use so will be contamiated every time they are used.
What type of water is used in creams?
Purified FBC to minimise chance of contamination
Whta are the other ingredients in creams that are non-therapeutic?
Lipid vehicle, cosolvent e.g. ethanol to help dissolve drug w/o, o/w emulsifier pH buffer for drug stability Humectant to prevent moisture loss Antioxidant to dtabililse penetration enhenacer DMSO Moisturoser and Lubricanr to improve cosmetic properties.
5 steps to preparing a cream:
1) heat hydrophobic and hydrophilic ingredients separately
2) mix at the same temperature
3) put energy into the system to form the stable cream
4) adjust the weight
5) active drug is dissolved in appropriate phase ot added to the prepared cream by geometric dilution.
What are GELS?
These are transparent, smei-solids (con sometimes be solid but not often)
Have a high water content
little or no oil (non-greasy)
Continuous 3D structure - solid-like properties.
What are in Hydrophobic gels?
These are oleogels
liquid paraffin and silica/alumminium/zinc soaps
What are in hydrophilic gels?
These are Hydrogels
Glycerol/propylene glycol and tragacnth/starch/cellulose, carboxyvinyl
WHat are the Tpes of gels?
Flocculated gels
Floc of Clays
Lyophilic gles (readily dispersed)
Irreversible Gels
What are flocculated gels?
Semi-solid
Particels associate and act as solid when not disturbed. Putting energy in will make the gel flow by breaking the weak association between molecules.
What are floc of clays?
Semi-solids
These have charges +ive and -ive
The layers assocaite together to form a solid-like structiure - layer stacking
Again putting energy in will break the bonds as they are weak enough,giving the semi-solid properties
What are lyphilic gels?
semi-solids
Network formed by entanglement or attraction between molecules
Bonds include hydrogen bonds and van der waals.
Increased HEAT will break the bonds - thermogels
What are irreversible gels?
SOLIDS:
drying agents - due to water adsorbing properties. Takes water in to protect the area that to be dry.
What are the rheology of Semi solids?
The flow of semi solids is complex.
they are prone to structural break-down
Prone to thixotropy - become less viscous when subjected to stress - gels become temporary less viscous
Prone to viscoelasticity - viscous and elastic properties deending on stress.
