EMULSIONS, SUSPENSIONS AND OTHER DISPERSE SYSTEMS Nahed HEGAZY, PhD
A disperse system consists essentially of one component, the disperse phase, dispersed as particles or droplets throughout another component, the continuous phase. Emulsions and suspensions are disperse systems; that is, a liquid or solid phase is dispersed in an external liquid phase. While emulsions are sometimes formulated from oily drugs or nutrient oils their main function is to provide vehicles for drug delivery in which the drug is dissolved in the oil or water phase. Suspensions, on the other hand, are usually prepared from water insoluble drugs for delivery orally or by injection, usually intramuscular injection.
By definition, dispersions in which the size of the dispersed particles is within the range 10-9 m (1 nm) to about 10-6 m (1 µm) are termed colloidal. However, the upper size limit is often extended to include emulsions and suspensions, which are very polydisperse systems in which the droplet size frequently exceeds 1 µm but which show many of the properties of colloidal systems. Many natural systems, such as suspensions of microorganisms, blood and isolated cells in culture, are also colloidal dispersions.
PHYSICAL PROPERTIES OF WELLFORMULATED SUSPENSIONS AND EMULSIONS The product must remain sufficiently homogenous for at least the period between shaking the container and removing the required amount. The sediment or creaming produced on storage, if any, must be easily resuspended by moderate agitation of the container. The product may be required to be thickened in order to reduce the rate of settling of the particles or the rate of creaming of oil globules. The resulting viscosity must not be so high that removal of the product from the container and transfer to the site of application are difficult. Any suspended particles should be small and uniformly sized in order to give a smooth, elegant product, free from a gritty texture.
CLASSIFICATION OF COLLOIDS Colloids can be broadly classified as: o lyophobic (solvent-hating) (= hydrophobic in aqueous systems) o lyophilic (solvent liking) (= hydrophilic in aqueous systems). [When the solvent is water the terms hydrophobic and hydrophilic are used].
Emulsions and suspensions are disperse systems a liquid or solid phase dispersed in an external liquid phase. o The disperse phase is the phase that is subdivided. o The continuous phase is the phase in which the disperse phase is distributed. Emulsions and suspensions are intrinsically unstable systems that require stabilisers to ensure a useful lifetime.
Emulsions exist in many forms: o oil-in-water (o/w) o water-in-oil (w/o) o oil-in-oil (rare) (o/o) o a variety of multiple emulsions such as water-in-oil-in-water (w/o/w) systems and oil-in-water-in-oil (o/w/o) systems.
OIL-IN-WATER (O/W) EMULSION
WATER-IN-OIL (W/O) SYSTEM
WATER-IN-OIL-IN-WATER (W/O/W) EMULSION
Main types of colloidal systems Type Disperse phase Continuous phase o/w emulsion Oil Water w/o emulsion Water Oil Suspension Solid Water or oil Aerosol Solid or liquid Air
COLLOID STABILITY Water-insoluble drugs in fine dispersion form lyophobic dispersions. Because of their high surface energy they are thermodynamically unstable and have a tendency to aggregate. Aggregation is a general term signifying the collection of particles into groups. Emulsions and aerosols are thermodynamically unstable two-phase systems which only reach equilibrium when the globules have coalesced to form one macro-phase, when the surface area is at a minimum.
COALESCENCE (BREAKING OR CRACKING) This problem arises when the dispersed globules come together and coalesce to form larger globules. o As this process continues, the size of the globules increases, making it easier for them to coalesce. This eventually leads to separation of the oil and water phases. o For cracking to occur, the barrier that normally holds globules apart has to break down (interfacial film destruction). Cracking is the most serious kind of physical instability of an emulsion. Cracking of an emulsion usually renders it useless. In creams, the problem of cracking may show up as tearing. This is a process where one phase separates and appears like drops on top of the cream.
SOME OF THE FACTORS THAT CONTRIBUTE TO CRACKING ARE AS FOLLOWS: Insufficient or wrong kind of emulsifier in the system. Addition of ingredients that inactivate the emulsifier. Incompatible ingredients may show their effect over a period of time. An example of such an incompatibility will be to use large anions in the presence of cationic emulsifier. Presence of hardness in water. The calcium and magnesium present in hard water can replace a part of the alkali soap with divalent soap. Since these soaps form different kinds of emulsions, phase inversion usually takes place. Low viscosity of the emulsion
Exposure to high temperatures can also accelerate the process of coalescence. This is due to the fact that at an elevated temperature, the collisions between the globules can overcome the barrier to coalescence, thereby increasing the chance that a contact between two particles will lead to their fusion. Temperature may have an adverse effect on the activity of emulsifiers. Conversely, a reduction in temperature to the point that the aqueous phase freezes also will break the emulsion. An excessive amount of the internal phase makes an emulsion inherently less stable because there is a greater chance of globules coming together.
Suspension particles achieve a lower surface area by flocculating or aggregating: they do not coalesce. Flocculation Flocculation involves the aggregation of the dispersed globules into loose clusters within the emulsion. The individual droplets retain their identities but each cluster behaves physically as a single unit. The presence of a high charge density on the dispersed droplets will ensure the presence of a high energy barrier and thus reduce the incidence of flocculation.
In dispersions of fine particles in a liquid (or of particles in a gas) frequent encounters between the particles occur due to: Brownian movement Creaming Sedimentation Convection.
An emulsion is said to cream when the oil or fat rises to the surface, but remains in the form of globules, which may be redistributed throughout the dispersion medium by shaking. An oil of low viscosity tends to cream more readily than one of high viscosity. Increasing the viscosity of the medium decreases the tendency to cream.
The rate of creaming depends on; The difference in density between the dispersed particles and the dispersion medium, The particle radius, a, and The viscosity of the dispersion medium η.
According to Stokes law the rate of sedimentation (or creaming) of a spherical particle, ν, in a fluid medium is given by v = 2ga 2 (ρ 1 ρ 2 )/ 9η where ρ 1 is the density of the particles, ρ 2 is the density of the medium and g is the gravitational constant.
Creaming of an emulsion or sedimentation of a given suspension can be reduced in several ways: By forming smaller particles (a ) By increasing the viscosity of the continuous phase (η ) By decreasing the density difference between the two phases (ideally ρ 1 ρ 2 )
The basic difference between creaming and cracking is that the globules ; In creaming do not coalesce to form larger particles. Therefore, creaming is a less serious problem and most preparations that show creaming can be shaken to redisperse the internal phase to its original state. In cracking come together and coalesce to form larger globules. As this process continues, the size of the globules increases, making it easier for them to coalesce. This eventually leads to separation of the oil and water phases. For cracking to occur, the barrier that normally holds globules apart has to break down (interfacial film destruction).
FORCES OF INTERACTION BETWEEN COLLOIDAL PARTICLES There are five possible types of force between colloidal particles: Electrostatic forces of repulsion van der Waals forces or electromagnetic forces of attraction Born forces essentially short-range and repulsive Steric forces, which are dependent on the geometry and conformation of molecules (particularly macromolecules) at the particle interface Solvation forces due to changes in quantities of adsorbed solvent on the very close approach of neighbouring particles.