Colloidal Dispersions

When two different substances are mixed together so that they mingle intimately, a two component system is produced. When one component is distributed uniformly throughout the second, the first component is called the dispersed phase and the second, the dispersion medium or continuous phase. Either phase may be solid, liquid, or gas.

Frequently in pharmacy a solid substance is dispersed in a liquid, usually water, and the resulting product may have the characteristics of either a molecular dispersion (true solution), a colloidal dispersion, or a coarse dispersion depending on the particle size of the dispersed solid. In true solutions the dispersed particles are ions or small molecules having particle size less than 1 nanometer (nm). In colloidal dispersions the particles are either single, large molecules of high molecular weight (macromolecules) or aggregates of smaller molecules with diameters between 1 nm and 500 nm in size (0.001 – 0.5µ). In coarse dispersions the particles are greater than 500 nm in diameter. Note that the particle size ranges given are not rigid and overlap does occur between each dispersion class.

The dispersed phase of a colloidal dispersion may be classified as being either lyophilic (solvent-loving) or lyophobic (solvent-hating). If the solvent is water these classifications are termed by hydrophilic and hydrophobic, respectively.

Molecules of a hydrophilic colloid have an affinity for water molecules and when dispersed in water become hydrated. Hydrated colloids swell and increase the viscosity of the system, thereby improving stability by reducing the interaction between particles and their tendency to settle. They may also possess a net surface electrical charge. The charge sign depends on the chemical properties of the colloid and the pH of the system. The presence of a surface charge produces repulsion of the charged particles and thus reduces the likelihood that the particles will adhere to one another and settle. Some examples of hydrophilic colloids used in pharmacy are acacia, methylcellulose, and proteins, such as gelatin and albumin.

A hydrophobic colloid has little or no affinity for water molecules in solution and produces no change in system viscosity. The particles may carry a charge, however, due to the adsorption of electrolyte ions from the solution. The dispersion of such particles is due to mutual repulsion of like charges and Brownian movement.

Neutralization of the particle charge may occur by addition of ions of opposite charge. The neutralized particles, which possess high surface free energy, cling together resulting in a precipitate. Most important is the influence of charge type and valence of the ions added. Their effect is summed up in the Schulze-Hardy Rule which states, first, that the effectiveness of an electrolyte is determined primarily by the nature of the ion opposite in charge to the colloidal particles, and second, as the valence of this ion increases, the effectiveness of the electrolyte increases markedly. Thus, for a negatively charged hydrophobic colloid such as arsenous sulfide, aluminum chloride is about 10 times more effective than magnesium chloride, and 500 times more effective than sodium chloride in causing the colloid to precipitate. Other examples of substances which form hydrophobic colloids in water are silver iodide, hydrated ferric oxide, sulfur, and gold.

Colloid dispersions exhibit several properties. Among these are the scattering of a light beam directed through a colloidal dispersion. This is known as the Tyndall effect and its magnitude is due to the size and number of particles present. When observed under ambient light, colloidal dispersions may appear translucent, opalescent or cloudy depending on the type of colloid and the degree of particle concentration and dispersion.

Under a microscope colloidal particles may be seen to “dance” or move at random. This is known as Brownian movement and is due to bombardment of the colloidal particles by molecules of the dispersion medium. Brownian movement is usually observed when particles are below 5µ in size.

The presence of a charge on colloidal particles gives them electrical properties. When exposed to an electrical potential colloids can be forced to migrate toward the electrode of opposite charge. This is known as electrophoresis and may be used to separate a mixture of colloidal substances such as proteins.

Colloids do not pass through a semi-permeable membrane. Thus, when a protein solution such as albumin is placed into a cellophane sac and submerged into water, water molecules will enter the sac to dilute the albumin molecules which cannot diffuse out. This principle explains the role of human serum albumin in maintaining the osmotic pressure of blood. The principle is also operational in the kidney where ions and small molecules are filtered out of the blood across the glomerular membrane but the macromolecular serum proteins are retained. Sterilization of injections is sometimes performed by filtration through a synthetic membrane having a mean pore size of 0.22µ (220 nm). It is important to realize that colloidal injections may not be sterilized by this method unless the particles are smaller than the mean pore size of the membrane.

Since a uniform dispersion of particles is important for the diagnostic and therapeutic effectiveness as well as the safety of administration of pharmaceutical colloids, stability against settling or coprecipitation is an important consideration. The addition of a hydrophilic colloid to a hydrophobic one causes the hydrophilic colloid to adsorb onto and completely surround the hydrophobic particles which then take on some of the properties of the hydrophilic colloid. The hydrophilic colloid shields the hydrophobic system from the destabilizing effects of electrolytes; thus the hydrophilic substance is called a “protective colloid”. Stability of such a system is enhanced, because in order to precipitate the hydrophobic colloid, both the protective solvent sheath surrounding it and the electric charge must be removed. Gelatin and methylcellulose derivatives are commonly used as protective colloids.

Sometimes in pharmaceutical formulations buffer salts are added to maintain a pH required for product stability. Occasionally such buffers may contribute to potential instability by forming insoluble salts with metallic ions. This problem may occur especially with phosphate buffers since most heavy metal phosphates are insoluble. If an insoluble phosphate salt precipitates from a colloidal dispersion, it may co-precipitate the colloidal particles along with it. To prevent this phenomenon from occurring, chelating agents may be used that will preferentially complex the metal ions, and thus prevent them from reacting with the phosphate. Alternatively, nonphosphate buffers may be substituted for phosphate buffers, when feasible, to prevent the instability.