Topical preparations

Question 1

Skin functions

Answer 1

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.

Question 2

Applications of the skin

Answer 2

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

Question 3

Targets within the skin

Answer 3

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

Question 4

Factors affecting delivery

Answer 4

Skin age
Skin condition
Skin region- plantar, palmar, scrotal, scalp, arm, leg, trunk
Skin metabolism
Species (testing topical formulations)

Question 5

Topical semi-solid formulation definition

Answer 5

Semi-solid preparations for cutaneous application are intended for local or transdermal delivery of active substances, or for their emollient or protective action.

Question 6

Formulation of vehicles

Answer 6

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

Question 7

Ointments

Answer 7

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

Question 8

Ointment bases- hydrocarbons

Answer 8

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

Question 9

Ointment bases- fats and fixed oils

Answer 9

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

Question 10

Ointment bases- silicones

Answer 10

Water repellant

Used in barrier creams to protect against water soluble irritants

Question 11

Ointment bases- absorption bases

Answer 11

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

Question 12

Ointment bases- emulsifying bases

Answer 12

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)

Question 13

Ointment bases- water soluble bases

Answer 13

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

Question 14

Preparing ointments

Answer 14

Insoluble ingredients must be finely powdered

Medicament incorporated into base by geometric dilution

Question 15

Pastes

Answer 15

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

Question 16

Creams

Answer 16

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

Question 17

Phases of creams

Answer 17

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.

Question 18

Emulsifying waxes and ointments

Answer 18

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

Question 19

Emulsifiers

Answer 19

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.

Question 20

Stabilising emulsions

Answer 20

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.

Question 21

Hydrophilic creams (oil in water creams)

Answer 21

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

Question 22

Preservation of creams

Answer 22

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

Question 23

Other non-therapeutic ingredients of creams

Answer 23

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

Question 24

Preparing creams

Answer 24

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

Question 25

Gels

Answer 25

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

Question 26

Types of gels

Answer 26

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

Question 27

Rheology

Answer 27

Semi-solid topicals show complex rheological properties

Prone to structural breakdown, thixotropy and viscoelasticity