Properties of Colloids and Coarse Dispersions
Colloids are dispersions of solid particles in a fluid. The particle size of the dispersed material is between 1 nm and 0.1 micrometer. This small size results in material which does not sediment under normal conditions. The material can be caused to sediment if put under the additional force generated in a centrifuge. Ultracentrifugation is a means of separation of colloidal particle by size. This process is often used in the preparation of proteins.
Suspensions may be defined as preparations containing finely divided drug particles (between 1 and 50 micrometers in diameter) distributed uniformly throughout a fluid or semisolid vehicle. These particles are large enough to sediment under the influence of gravity. A well-made commercial suspension will have additional ingredients called excipients that act to improve the stability of the dispersion. The suspension should settle slowly, be readily redispersed upon gentle shaking, pour readily and maintain the particle size of the ingredients throughout long periods of storage.
Extemporaneously prepared suspensions should also have these same characteristics. The lone difference being that they do not have to be stable for as long a period of time as they are made by a pharmacist for immediate use on a specific patient.
Stokes Law and Sedimentation Rate
Gravity is the great enemy of all suspensions but other factors can also influence the stability of the final product. Stokes Equation is an empirical relationship which takes into account the forces which work on dispersed systems like suspensions and emulsions.
Stoke said that the rate of sedimentation of particles in a fluid is a function of the size of the particle, the force of gravity, the thickness or viscosity of the fluid and the density difference between the particle and the fluid. When Stoke's Law is applied to an emuslion the equation yields a negative sedimentation rate which means that the globules are moving up to the surface because of the density difference between oil and water.
dx/dt = d2(rho1 - rho2)g/18Viscosity
When particles of a suspension come close together they can form aggregates called flocculates which will settle more rapidly. To prevent that we often coat the particle with a charged surfactant. The charge (Zeta potential) acts to keep the particles separate and prevent flocculation. Sometimes we want to have flocculation because the sediment that the flocculates make are easy to resuspend. In that case we add salt to overcome some of the Zeta Potential and allow the particles to come close enough together to weakly attach to each other. Deflocculated suspensions settle slower but when they do settle they often form a tightly packed sediment called a cake which cannot be resuspended.
Hints for extemporaneously preparing a suspension - Mix the powders together first. Include dry suspending agents with the powders. Add a small amount of liquid that will wet the powders. You can use liquid suspending agents to do this. Triturate the powders with this liquid to form a thick paste. Continue to triturate to reduce particle size and get all the powder evenly distributed. Now gradually add the rest of the liquid. Add alcohol and salts last. They both hurt the ability of most thickening agents or suspending agents to stabilize the suspension.
An emulsion is a dispersion in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible. Because of the large increase in surface free energy caused in the production of an emulsion the use of surfactants or flim formers is important as a way to stabilize the product. Surfactants lower the interfacial tension between the oil and water. This lowers the amount of energy needed to form the emulsion. The surfactant also forms a rigid film over the globules preventing them from coming together after they are formed. Material used for this purpose include carbohydrates such as acacia, protein such as gelatin, cholesterol from egg yolk, finely divided powder such as bentonite, and surfactants such as Tween and Span.
Extemporaneous Preparation. A common way of making an emulsion is to use Acacia, oil and water in the ration of 1 part acacia to 4 parts oil and 2 parts water. Regardless of the total water in the prescription the primary emulsion is made based on the total oil and oil soluble ingredients. This is used to make the primary emulsion. After it is formed the other water soluble ingredients and the rest of the water can be added. It is important to add alcohol and salt last.