Emulsions, suspensions and other disperse systems

5 Applications of colloid stability theory to other systems 265 

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. An increasing number of modern delivery systems are suspensions - of liposomes or of polymer or protein microspheres, nanospheres or dendrimers, hence the need to understand the formulation and stabilization of these systems. Pharmaceutical emulsions and suspensions are in the colloidal state, that is where the particles range from the nanometre size to visible (or coarse) dispersions of several micrometres. 

After a general introduction to colloidal systems (these being disperse systems with particles below about 1 m in diameter) this chapter introduces the main types of emulsions namely, 

The chapter should allow an appreciation of the factors leading to emulsion stability and physical instability, including flocculation and coalescence. Approaches to the formulation of emulsions to provide vehicles for drug delivery and parenteral nutrition (the main uses in pharmacy) should be understood. 

The chapter then deals with aqueous and nonaqueous pharmaceutical suspensions and their formulation and forms of instability, which are principally sedimentation, flocculation and caking. Finally, some newer colloidal systems used pharmaceutically will be discussed. 

---

Chapter 7 Emulsions, suspensions and other disperse systems... 

Phenomena at Liquid Interfaces. The area of contact between two phases is called the interface three phases can have only aline of contact, and only a point of mutual contact is possible between four or more phases. Combinations of phases encountered in surfactant systems are L—G, L—L—G, L—S—G, L—S—S—G, L—L, L—L—L, L—S—S, L—L—S—S—G, L—S, L—L—S, and L—L—S—G, where G = gas, L = liquid, and S = solid. An example of an L—L—S—G system is an aqueous surfactant solution containing an emulsified oil, suspended soHd, and entrained air (see Emulsions Foams). This embodies several conditions common to practical surfactant systems. First, because the surface area of a phase iacreases as particle size decreases, the emulsion, suspension, and entrained gas each have large areas of contact with the surfactant solution. Next, because iaterfaces can only exist between two phases, analysis of phenomena ia the L—L—S—G system breaks down iato a series of analyses, ie, surfactant solution to the emulsion, soHd, and gas. It is also apparent that the surfactant must be stabilizing the system by preventing contact between the emulsified oil and dispersed soHd. FiaaHy, the dispersed phases are ia equiUbrium with each other through their common equiUbrium with the surfactant solution. 

Foams are agglomerations of gas bubbles separated from each other by thin films (5). Mainly, the problem is concerned with one class of colloidal systems —gas dispersed in liquid—but liquid dispersed in gas, solids dispersed in liquid (suspensions), and liquids dispersed in liquids (emulsions) cannot be ignored. The dispersion of a gas into a liquid must be studied and observed by the food technologist to improve the contact between the liquid and gas phases, the agitation of the liquid phase, and most important, the production of foam 10). 

Suspension stability is governed by the same forces as in other disperse systems such as emulsions. There are differences, however, as coalescence obviously cannot occur in suspensions the adsorption of stabilising polymers and surfactants may also occur in a different... 

It would be inappropriate not to mention that particle size and particle size distribution are important parameters related to the stability of emulsions, suspensions and dispersions. In general, the stability of these systems decreases with increasing particle size or size distribution. Of course, variables other than particle collisions and sedimentation such as electrokinetics, dispersants, steric stabilizers and others also affect stability. In short, the variables affecting stability can be divided into those factors that cause particles to come together and those factors that make the particles stick together, or stay apart (i.e. factors related to attractive or repulsive forces). 

Disperse systems can be classified in various ways. Classification based on the physical state of the two constituent phases is presented in Table 1. The dispersed phase and the dispersion medium can be either solids, liquids, or gases. Pharmaceutically most important are suspensions, emulsions, and aerosols. (Suspensions and emulsions are described in detail in Secs. IV and V pharmaceutical aerosols are treated in Chapter 14.) A suspension is a solid/liquid dispersion, e.g., a solid drug that is dispersed within a liquid that is a poor solvent for the drug. An emulsion is a li-quid/liquid dispersion in which the two phases are either completely immiscible or saturated with each other. In the case of aerosols, either a liquid (e.g., drug solution) or a solid (e.g., fine drug particles) is dispersed within a gaseous phase. There is no disperse system in which both phases are gases. 

Just as with emulsions and foams, suspensions can exist with additional dispersed phases present. They may contain, in addition to solid particles and a continuous liquid phase (and possibly a stabilizing agent), emulsified droplets and/or gas bubbles. Figure 2.4 (in Section 2.2.1) shows photomicrographs of a practical suspension that contains suspended oil droplets in addition to the particles. The terminology used to describe such systems can become confusing. Consider an aqueous dispersion of solid particles and emulsion droplets. If the solid particles are adsorbed on the emulsion droplets then it is an emulsion that also contains solids. If, however, the particles and droplets are not mutually associated then the system is at once a suspension and an emulsion. Which term is used becomes a matter of choosing the most appropriate context frequently one or the other is considered to be the primary dispersion while the other phase is considered to be an additive or a contaminant. 

For monodisperse or unimodal dispersion systems (emulsions or suspensions), some literature (28-30) indicates that the relative viscosity is independent of the particle size. These results are applicable as long as the hydrodynamic forces are dominant. In other words, forces due to the presence of an electrical double layer or a steric barrier (due to the adsorption of macromolecules onto the surface of the particles) are negligible. In general the hydrodynamic forces are dominant (hard-sphere interaction) when the solid particles are relatively large (diameter >10 (xm). For particles with diameters less than 1 (xm, the colloidal surface forces and Brownian motion can be dominant, and the viscosity of a unimodal dispersion is no longer a unique function of the solids volume fraction (30). 

An important common feature of macroion solutions is that they are characterized by at least two distinct length scales determined by the size of macroions (an order up to lOnm in the case of ionic micellar solutions) and size of the species of primary solvent (water molecules and salt ions, i.e. few Angstroms). Considering practical colloidal macro-dispersions, like foams, gels, emulsions, etc., usually we are dealing with as many as four distinct length scales molecular scale (up to lnm) that characterizes the species of the primary solvent (water or simple electrolytes) submicroscopic or nano scale (up to lOOnm) that characterizes nanoparticles or surfactant aggregates called micelles microscopic or mesoscopic scale (up to lOO m) that encompasses liquid droplets or bubbles in emulsion and foam systems as well as other colloidal suspensions, and macroscopic scale (the walls of container etc). 

Suspension, Dispersion, and Emulsion Polymerizations in Water (Heterogeneous System) 5. Other Special Solvents 3710... 

---