![]() ![]() The emulsion phases are pumped together under high pressure into a small volume or through a small orifice – the interaction chamber where pressures in the tens of thousands of PSI create very high shear forces (Figure 3).Įmulsions with an average droplet size as small as 0.2 µm can be formed this way, which is significant as these are amenable to sterilization by filtration through a 0.2 µm filter.Įmulsions are prepared by adding one phase to the other over time, with one or both phases containing emulsifier, and applying shear. High-pressure homogenizers are readily scaled and can also produce emulsions with nano-sized droplets. To make even smaller nano-sized droplets, at small scale, ultrasonic devices can be used, but they are generally not practical to scale up. These operate by pumping the emulsion phases through the narrow gap between a perforated cylinder (the stator) and the blades of a rapidly rotating stirrer housed inside it (the rotor) where the forces are sufficient to make droplets as small as around 1 µm (Figure 2). High shear rotor-stator mixers are commonly used. Simple paddle-type mixers are suitable when the required droplet size is above ~10 µm but to make smaller droplets, higher shear is generally required. This energy usually comes from mechanical shear provided by various types of mixers, and the final droplet size of the emulsion is dependent on not only the chemistry but also the amount of energy applied. The first corollary of this is that emulsification is rarely a spontaneous process, and hence requires the input of energy. Without going deeply into the relative energetic contributions, the free energy of emulsification is positive. The Gibb’s free energy change, ΔG, on forming an emulsion from two bulk liquids is given by the familiar equation: ΔG=ΔH–TΔS, where ΔH is enthalpy change, T is temperature, and ΔS is entropy change.ġ00 ml of an o/w emulsion containing 10% w/w of oil in the form of 1 µm droplets, contains 2 x 1013 droplets, having a combined surface area of 60 m2 Therefore, they remain at the droplet interface where they can provide a barrier to droplet coalescence. The stabilizing particles are selected or engineered to have a contact angle with water of close to 90° so that they are wetted by the continuous and dispersed phases. A Pickering emulsion is one stabilized with ultrafine solid particles rather than molecular emulsifiers. Most emulsions contain droplets with a mean diameter of >1µm, however mini-emulsions and nano-emulsions can be formed with droplet sizes in the 100-500 nm range, and with proper formulation, highly stable microemulsions can be prepared having droplets as small as a few nanometers. These emulsion types are shown schematically in Figure 1. A triple emulsion with water dispersed in oil droplets, with themselves then dispersed in water, is referred to as a water-in-oil-in-water emulsion (w/o/w) and the less common reverse analogue is termed oil-in-water-inoil (o/w/o). More complex “triple” emulsions have dispersed droplets that contain smaller droplets of continuous phase material. Emulsifiers reduce the energy required to break the dispersed phase into droplets and prevent them from coalescing by generating a repulsive force or a physical barrier between them.Įmulsions that are formed by dispersing a water-immiscible liquid into an aqueous phase are termed oil-inwater (o/w), while those having aqueous droplets dispersed in a continuous oil phase are termed water-in-oil (w/o). ![]() Emulsions also contain emulsifiers – materials that concentrate at the phase interface to lower the interfacial tension. In its simplest form, an emulsion is a mixture of two immiscible liquids (usually an organic “oil” and water) in which one liquid (the dispersed phase) is in the form of microscopic droplets dispersed in the other (continuous) phase. Pharmaceutically inactive and simply provide an elegant vehicle for an API formulation. ![]()
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