Methods Of Formulation I Flashcards
What is a disperse system
A system made of a dispersed/internal phase (particles or droplets) dispersed in another component (the continuous phase)
Define: Colloidal dispersion Coarse dispersion Sol Emulsion Foam Aerosol
A term used when the droplets are between 1nm-1micrometer
A term used when the droplets are above 1micrometer in size. Often relates to emulsions and suspensions
A colloidal dispersion of solid particles in a liquid
A mixture of two immiscible liquids
When gas particles are trapped in a liquid or a solid
A solid or liquid dispersed in a gas
Detail the characteristics of a lyophobic sol
(A colloid that is solvent hating)
Include details of the effect of electrolytes, stability, formation, viscosity
These colloids are very sensitive to electrolytes leading to irreversible aggregation. Depends on the type and valency of counter ion and the concentration of the electrolyte
Stability is controlled by the charge of the particles
They are usually made of metals, inorganic crystals. Are never formed spontaneously. Particles remain dispersed fur to electric repulsion
Low viscosity, particles unsolvated and usually symmetric
Detail some characteristics of a lyophilic sol
Solvation plays an important role in stability. Generally stable in the presence of electrolytes except when the electrolytes are at high concentrations (desolation of lyophilic molecule). Proteins more sensitive at the pI
Stability is controlled by the charge and salvation of particles
Are usually formed of proteins, macromolecules (which disperse spontaneously in the solvent). Free energy of formation is negative - they have a stable thermodynamic system hence they can firm spontaneously.
Usually have a high viscosity (when the concentration is high in some cases a gel can form). Particles are solvated and usually asymmetric.
Give some examples of lyophilic (hydrophilic) sols
Polymers, gums (tragacanth, methylcellulose) and proteins
Give some examples of hydrophobic colloids
Particles formed by aggregation of smaller particles (eg protein aggregates) or breakdown of larger particles into colloidal dispersions (emulsions, suspensions)
How do we prepare lyophilic colloidal systems
The affinity of the particles to the solvent leads to spontaneous formation of the colloidal dispersion
(This is the easy one)
How do we prepare lyophobic colloidal systems
There are 2 methods: dispersion and condensation
Dispersion involves the breakdown of coarse material using a colloidal mill or ultrasonic treatment (this is how we prepare emulsions or graphene suspensions)
Condensation involved the rapid production of supersaturayed solutions causing the formation of colloidal particles (which won’t precipitate). This often occurs during chemical reactions such as colloidal silver iodide. A change of solvent can also produce colloidal particles
Which three techniques can be used to purify disperse systems
Dialysis - uses a membrane with pores at an exactly specified size which only allow molecules smaller than the pore size to cross. We use daltons to determine which ones can cross as the molecular weight determines the particle size
Ultrafiltration- uses the same process as dialysis except the solvent is put under pressure to speed the diffusion process up - the solutebwill cross the membrane faster
Electrodialysis - if the molecules are charged, we can apply an electric field to the solution to make the molecules move across the membrane
Bottom line - all follow the same filtering process, the latter two, however are sped up versions
Where do colloids end up after purification
They stay on the same side of the membrane - the impurities cross it
Give a summary of the properties of colloidal dispersions (inc. typical size of particles, shapes,light scattering
The size range of colloidal particles is wide and are often polydisperse.
The shape varies - they can be spherical, rods, ellipsoid etc
As colloids are large, they scatter light (somethingbwe can use to determine their exact size)
Particles >0.5micrometres will sediment under gravity, smaller ones will require centrifugation
How do we find out the size distribution of a colloidal particle
This is given by their pdi- polydispersity index
What are coagulation and flocculation and what causes them
They are related to the physical stability of colloidal systems.
Coagulation- permanent contact of particles
Flocculation - temporary contact of particles
They are caused by brownian movement which cause collisions between the dispersed particles. Whether they form floccs or coagules will depend on their forces of attraction and repulsion
What is DLVO and when is it used
A theory which explains the aggregation of aqueous dispersions by describing the force between charged surfaces interacting through a liquid medium. It is used mainly with lyophobic colloids and relies on repulsion (elecyrostatic forces, born (short range) and attraction (van der waals)
What happens to hydrophilic compounds in the presence of a hight concentration of electrolytes
Theyr lose their salvation water to these ions and will salt out
What is a solvation force and what does it relate to
The amount of adsorbed solvent changes on the approach of neighboring particles
They relate to hydrophobic colloids
What is a surfactant and how does it work
An amphipathic molecule (they have both lyophilic and lyophobic parts). They are surface active and move at the interface between 2 phases allowing the lyophobic part to evade contact with the solvent
What are micelles and how do they work
After covering all the interfaces between the solvent and solute and the surfavtamt concentration continues to increase these surfactants begin to form micelles. These are only present above the critical micelle concentration and, once this has occurred, there is no further reduction in surface tension due to the presence of the surfactant
Name the 4 categories of surfactants (including examples) and explain why they are categorised this way
They are categorised by the differences in their hydrophilic heads
Anionic (sodium lauryl sulphate SLS)
Cationic (benzalkonium chloride)
Non-ionic (polysorbates)
Zwitterionic (CHAPS, phosphatidylcholine)
What are they typical characteristics of a micelle
Spherical, composed of 50-100 surfactant molecules and 3nm in diameter
In which circumstances are non-ionic and cationic surfactants used
Non-ionic : parenteral use as they are less toxic
Cationic - external bactericides
Which way do micelle surfactants face in aqueous solvent and which way do they face in organic solvent
Hydrophilic heads face out to the solvent in aqueous solvent
In organic solvent they are called inverted micelles as the hydrophobic tail faces out to the solvent
Why are surfactants used in pharmacy
They are used widely in formulation as they can improve wetting, stabilise emulsions and reduce absorption of mass at interfaces. Phenolic compounds such as cresol and thymol are frequently solubilised with surfactants to form a clear solution for disinfection
Non-ionic surfactants (polysorbate etc.) are used to prepare aqueous injections of the water soluble vitamins A,D,E and K
Micellar solutions of penicillin G are 2.5x more stable than the monomers ones
Surcaftants are also used as detergents
What is am emulsion and what do they require
A mixture of two immiscible liquids, one dispersed in the other. They require emulsifiers to facilitate their formation and stability. They have droplets from 01. to 100micrometers and are inherently unstable (like most disperse systems)
Give examples of some emulsifiers
Surfactants, polymers, Solid particles, phospolipids, wool fat, beeswax
In an oil in water emulsion which is the dispersed phase and which is the continuous phase
The oil is the dispersed phase and the water is the continuous phase
What is an inverted emulsion
An emulsion where the dispersed phase is water and a continuous phase is oil
When is an emulsion stable and how is this achieved
When the globules retain initial character and remain uniformly distributed throughout the continuous phase
This is achieved by using emulsifiers which form an interfacial film around droplets. For an oil in water emulsion this means that the hydrophobic droplets will be made hydrophilic
What causes emotions to crack
Any agent that destroys the interfacial film will crack the emulsion. This will happen in the presence of chemicals incompatible with the emulsifier, if there is baterial growth or change of temperature
When are emulsions used in pharmacy
To formulate creams, ointments and pastes
To administer oils/fat for iv nutrition
Particle size must be controlled to prevent embolism.
How do we increase emulsion stability
By reducing the droplet size - reduced probability of coalescence
Decreasing the density differences - limiting creaming
increasing the viscosity of the continuous space - slows the movement of particles hence reducing the probability of collision
How do we assess stability
Visualisation
Monitoring particle size over time using light scattering
Define coalescence, flocculation, creaming and phase inversion.
Coalescence - Small droplets combine to form larger ones -any electric charge on the particles should result in repulsion
Flocculation - droplets form clusters - this is the combined result of attractive and repulsive forces due to formation of the secondary minimum according to the DVLO theory
Creaming - The dispersed phase rises to the top in an oil in water emulsion or sinks to the bottom in a water in oil emulsion. This is the result of density differences between the phases. It can be redistributed but may result in in appropriate dosage.
Phase inversion - Emotions stabilise of non our emulsifying agents may undergo a phase inversion on heating
The choice of oil, emulsifyer and emulsion type used for emulsions depends on route of administration, clinical usability and toxicity
Which oil do we use for: External applications Oral emulsions Parenteral emulsions Emulsifiers
Liquid paraffin, soft or hard paraffin, turpentine oil or silicone oils
Castor oil or liquid paraffin
Limited choice - purified mineral oil for im injections, vegetable oil with long triglycerides
PS80, sorbitol, Pluronic 68, lectins (parenteral) cerimide, sls (topical)
Methylcellulose, aluminium hydroxide (oral)
How do we work out the hydrophilic lipophilic balance of an emulsifier
A combination of emulsifiers is often used. As the HLB of the emulsifiers need to equate that of the oil phase, you need to work out the HLB of both oil phases then the percentage of the difference of surfactants
What type of emulsions are creams (usually)
Oil in water. To form the cream, sparingly soluble fatty amphiphiles are combined with more water soluble ionic surfactants. They are stabilised long term by the formation of a viscoelastic gel network phases trapping oil droplets and preventing their movement and interaction
What is the gel network theory of emulsion stability
A coherent explanation if how fatty ampipjiles and surfactants combined as emulsifiers not only stabilise these creams but also control their consistencies
How does swelling impact creams
Combinations of fatty alcohols and ionic surfactants exhibit phenomenal swelling.
Importantly, the swelling is electrostatic in nature as the surfactant interpose among the fatty alcohol molecules and electrostatic repulsion between the adjacent bilayers arises from the overlap of the electrical double layers.
Similarly to what was discussed for other dispersed systems, adding electrolytes eg. NaCl to creams reduces the electrostatic swelling between the bilayers, less repulsion, thus the gel network phase volume.
Are aerosols more or less stable than colloids
Less as they have a liquid continuous phase.
What are aerosols and how can they be achieved
Collodial dispersions of liquids or solids in gas.
They are achieved using pressurised containers containing liquefied gases as propellant
What is a foam
A coarse dispersion of the gas in a liquid which is present as thin films or lamellae of colloidal dimensions when the gas bubbles
Pure liquids don’t foam, how do we create them then?
Transient or unstable forms are obtained with short chain acids and alcohols which mildly surface active. Persistent forms are formed with surfactants
Why are foams thermodynamically unstable
Due to their vast interfacial area. The gas diffuses from small bubbles to larger ones (reduces surface area) Stability depends on their ability to drain and become thinner and the tendency to rupture in presence of stress (shaking, heat)
How are gels formed
By the aggregation of colloidal sol particles. The solid/semi solid system is ingerpenetrated by a liquid. Only a small percentage of the disperse phase is needed
What is a xerogel
The structure left behind when the liquid phase is removed from a gel
What is a lyophilic gel
One prepared with polymers (agarose)
Type 1 - gel is held together by covalent bonds between the macromolecules. They swell in water and are used for controlled release antibiotics. Example, poly(HEMA) crosslinked with EGDMA
Type 2 - held together with hydrogen bonds and are reversible dependent on temperature
What are lyophobic gels
A continuous flocclue.
Clays form gels by flocculation in a card house floc network. These gels are also called thixotropic gels as application of force will individualise the particles and break the structure
The forces holding these particles together are weak which gives rise to a secondary minimum.
Where are gels particularly used
Opthalmic preparations as they undergo gelation at body temperature and have bioadhesive properties
