Creams, ointments and gels Flashcards
What are creams and what are they used for?
- Creams are semi-solid preparations intended for external use
- For protective, therapeutic purpose
Properties of hydrophilic creams
• Aq phase as the continuous phase • O/W emulsions • Non-greasy texture • Water washable • Non-occlusive • Continuous phase evaporates (drug concentration in adhering film increases) • Topical administration of drugs
Most commonly used emulsifiers in creams
– Lipophilic amphiphiles, such as fatty alcohols, fatty acids
– Ionic water soluble surfactants
– Non-ionic water soluble surfactants
Creams - emulsifiers - ready made mixtures eg
– Aq cream(BP) Emulsifying Ointment 300g
Phenoxyethanol 10g
Purified Water to produce 1000g
Interaction of emulsifiers in water
• Long chain alcohols exist in 3 different polymorphs
– α-form: high temperature, come out first when cooled
– β-form and γ-form: can coexist, low temperature (including room temperature)
• Transition temperature of the lipid amphiphiles(long chain alcohol) is reduced when in the form of mixtures
– Pure cetyl or stearyl alcohol exists as β- and γ-crystaline polymorphs
– Cetostearyl alcohol exist as α-crystalline forms
• Formation of α-crystalline is the prerequisite to form liquid crystalline and swollen crystalline phases
Lamellar gel network theory
• α-Crystalline shows limited swelling in excess of water.
• After a small amount of surfactants is added, it swells significantly to form
a viscoelestic α-Crystalline gel phase.
• After heated to Tc, it transforms to a less swollen liquid crystalline state.
• The crystalline gel net work traps and immobilises the oil droplets, hence
stabilises the cream.
Interaction of emulsifiers in water
• α-crystalline forms waxy crystalline hydrates with limited swelling in presence of water
• In the presence of small amount of surfactants (alcohol to surfactant molar ratio 10-30 : 1), it forms α-crystalline gel phase
– Viscoelastic
– Associated with increased swelling
• The α-crystalline gel phase changes to a less swollen liquid crystalline form upon heating to Tc (gel liquid transition temperature)
• Upon cooling below Tc, it reverts back to the swollen gel phase – Tc is usually between 40-50°C for cetostearyl alcohol and other
commonly used amphiphiles in creams
– During manufacture process (high temperatures): liquid crystalline state. The cream is less viscous
– After manufacture, upon cooling, it hardens (more viscous), sometime the transition temperature is called ‘the setting temperature’
Microstructure of creams
- When water is freely movable, the viscosity is low. When water is trapped in the gel structure, the viscosity is increased.
• The dispersed oil droplets stabilised by – Monolayer emulsifier film
– Charge
• The viscoelastic continuous phase
– α-Crystalline gel phase: bilayers of fatty alcohol and surfactant separated by interlamellar fixed water (significant swelling)
– α-Crystalline hydrate (limited swelling) – Bulk continuous free water
Liquid emulsions
Oil droplets free moving, may coalesce, may flocculate, may move to form a cream layer
Creams (o/w)
Oil droplets are effectively immobilised in gel phase, no creaming, no coalescence, no flocculation
Specific emulsifier mixtures - Fatty alcohol with ionic emulsifiers
Fatty alcohol with ionic emulsifiers
– Extensive swelling: water layer is 10 times thicker than the carbon layer
– Electrically charged
– DLVO theory applies to adjacent bilayers (Emulsions
lectures)
– Addition of electrolytes will
• reduce the repulsion between adjacent bilayers (review diffuse double layer and DLVO theory)
• Reduce the volume of the lamallar gel-network phase • Reduced viscosity
Specific emulsifier mixtures - Fatty alcohol with PEO surfactants
• Fatty alcohol with polyoxyethylene (PEO) surfactants
– Swelling due to the hydration of the PEO chain
– Steric stabilisation: PEO chain extends into the water
layer
– At high temperature shortly after preparation: PEO chain less well hydrated, no gel phase formed, relatively more fluidic
– During storage at low temperature: PEO better hydrated, more swelling due to the formation of gel phase, more viscous
Specific emulsifier mixtures -Fatty acid mixed emulsifiers
Fatty acid mixed emulsifiers
– Fatty acids
• Polymorphisms
• Vanishing cream: appears to be vanishing when being applied, leaving a ‘non-greasy’ residue on the skin
– Stearate cream: stearic acids partially (10-40%) neutralised by alkali, e.g.
• Triethanolamine: forms swollen lamellar structure
• NaOH, or KOH
– Does not appear to form swollen lamellar structure;
– forms disordered interlinking bilayers of mixed emulsifiers (twisted ribbon), entrapping large amount of water
What are ointments
- Consists of a single-phase basis in which solids or liquids may be dispersed
- Highly viscous and moisture occlusive - emollient, protective and therapeutic effects
Gels
Semi-solid systems(usually)
• Liquid vehicle interacts with colloidal particles
• Bonds form between adjacent particles resulting in a 3-D network formation
• Continuous phase held between 3-D network
• Some forms of gels (e.g. hydrogels can hold ~90%
water)
• Gels usually thin after application of a small sheer stress, and are amenable to topical application
Types of gel
• Gelation of lyophilic colloids(polymers)
Type I
• Covalent bonds between the macromolecules
• Irreversiblesystem
• The cross linking system created by the polymer is not dissolvable
• Polymeric implants
• Sustained release of drugs
• Polymer: e.g. 2-hydroxyethylmethacrylate (HEMA) cross linked with ethylene glycol dimethacrylate
Type II
• Hydrogen bonds or VDW
• Heat-reversible (heating or cooling)
• Polymer: e.g. polyvinyl alcohol
Types of gel - Gelation of lyophobic colloids (sols)
• Gelation of lyophobic colloids (sols)
– Consist of floccules of small particles, e.g. • Bentonite
• Aluminium magnesium silicate
– Van der Waals forces (aluminium / magnesium
hydroxide)
– Electrostatic attraction between the particles
– When shear stress is applied (e.g. simple shaking), it turns to a lyophobic colloid (with lower viscosity)
– Thixotropy (gel-sol-gel transformation)
Gelling agents
• Semi-synthetic materials
– Methylcellulose (MC)
– Carboxymethylcellulose (CMC) – Hydroxyethylcellulose (HEC)
– Hydroxypropylcellulose (HPC)
– Hydroxypropyl methylcellulose (HPMC) - Higher clarity of gel than MC
• Natural gums – Acacia – Guar – Tragacanth (2 –5 %) • Mixture of water-insoluble and water-soluble polysaccharides • Negatively charged in aqueous solution – Xanthan – Alginate (1.5 –10 %)
• Clays
– Bentonite
– Aluminium magnesium silicate
• Synthetic materials
– Carbomer (carboxyvinyl polymer)
Gelling temperature (Tg)
Some polymer solutions turn to a gel at a given temperature, upon heating or cooling
• Poly vinyl alcohol solution turns to gel upon cooling
– Tg ≠ mp point of gelling agent
– Tg is usually quite broad
– Higher conc, ↑ Tg
– ↑ Tg suggests that a higher energy is required to break the structure of the gel network
• Concentrated Poloxamer solutions turn to gel upon heating
– -OH groups are better hydrated at low temperature
– Poloxamers form micelles at high concentrations (above CMC)
– Increasing temperature will result in more micelles being formed, which can compact together to form gels
Mechanisms of Carbomer uncoiling
• Convert the acidic molecule to a salt,e.g.
– addition of NaOH or KOH for aqueous or polar solvent systems
– addition of triethanolamine or diethanolamine for less polar or non-polar solvent systems
• The–COOH groups are converted to–COO-Na+ (Charged)
• electrostatic repulsion results in coil expansion (polymer swelling)
• Viscosity of the resultant gel depends on the extent of polymer opening
What are the emulsion types for aqueous and oily creams
– Aq creams: o/w emulsions
– Oily creams: w/o emulsions
What is the aqueous phase of a cream structured by?
– The aq phase of a cream is often structured by
• the addition of structuring materials, e.g. clay particles, polymers
• Forming lamellar gel network phases as a result of the interaction between some emulsifiers and water
Are creams miscible with anything?
• Essentially miscible with the skin secretion
What are the 3 different types of ointments?
• Hydrophobic Ointments
– Can absorb only small amounts of water
– Occlusive effect
- Typical bases: hard, liquid and light liquid paraffins, vegetable oils, animal fats, synthetic glycerides, waxes and liquid polyalkylsiloxanes
• Water-emulsifying Ointments
– Can absorb larger amounts of water
– Results in water-in-oil o roil-in-water emulsions
• Hydrophilic Ointments
– Bases are miscible with water, e.g. polyethylene glycols (macrogols) – May contain appropriate amounts of water
– Less emollient
