Pharmaceutical emulsions droplet size distributions

Techniques of emulsification of pharmaceutical products have been reviewed by Block [27]. The location of the emulsifier, the method of incorporation of the phases, the rates of addition, the temperature of each phase, and the rate of cooling after mixing of the phases considerably affect the droplet size distribution, viscosity, and stability of the final emulsion. Roughly four emulsification methods can be distinguished ... 

Other pharmaceutical applications have seen the SdFFF applied successfully to monitor droplet size distributions in emulsions, together with their physical state or stability. Some examples are fluorocarbon emulsions, safflower oil emulsions, soybean oil emulsions, octane-in-water emulsions, and fat emulsions. SdFFF is also able to monitor changes in emulsion caused by aging or by the addition of electrolytes. SdFFF has been used to sort liposomes, as unilamellar vesicles or much larger multilamellar vesicles, the cubosom, and polylactate nanoparticles used as drug delivery systems [41]. 

In the chemical industry (on the mega- as well as the micro-scale) fine emulsions have many useful applications in, e.g., extraction processes or phase transfer catalysis. Additionally, they are of interest for the pharmaceutical and cosmetic industry for the preparation of creams and ointments. Micromixers based on the principle of multilamination have been found to be particularly suitable for the generation of emulsions with narrow size distributions [33]. Haverkamp et al. showed the use of micromixers for the production of fine emulsions with well-defined droplet diameters for dermal applications [38]. Bayer et al. [39] reported on a study of silicon oil and water emulsion in micromixers and compared the results with those obtained in a stirred tank. They found similar droplet size distributions for both systems. However, the specific energy required to achieve a certain Sauter mean diameter was 3-1 Ox larger for the macrotool at diameters exceeding 100 pm. In addition, the micromixer was able to produce distributions with a mean as low as 3 pm, whereas the turbine stirrer ended up with around 30 pm. Based on energy considerations, the intensification factor for the microstirrer appears to be 3-10. 

Differences can be found not only in mean droplet sizes or specific energies required, but also in the width of droplet size distributions (Figure 20.16). High-pressure homogenization allows for the production of emulsions in the sub-micron range however, the droplet size distributions are rather broad. In contrast, membrane emulsification results in droplet size distributions that are extremely narrow. Hence products with well-defined characteristics (e.g. release kinetics) can be produced, as required in, e.g., pharmaceutical applications. 

Emulsions are dispersions of two immiscible liquids into each other. They are thermodynamically unstable, but the addition of surfactant molecules can provide significant kinetic stability. Emulsions are extensively used in food, cosmetic, and pharmaceutical industries, just to name a few. Because of the thermodynamic penalty, emulsion formation requires an energy input. In bulk systems, this can most easily be achieved by vigorous stirring or shaking of the whole oil/water/surfactant system. This approach leads to an pulsion with broad droplet size distribution. Microfluidics allows for the minimization of polydispersity and the creation of droplets that are virtually identical in size. 

An emulsion is a dispersed system where one liquid phase is finely subdivided as globules or droplets and uniformly distributed in the other liquid phase. The practical application of emulsions and their technology applies to pharmaceutical and cosmetic formulations. The usual globular or droplet sizes range from 0.1 to 10 pm. 

One of the earliest uses of power ultrasound in processing was in emulsification. If a bubble collapses near the phase boundary of two immiscible liquids, the resultant shock wave can provide a very efficient mixing of the layers. Stable emulsions generated with ultrasound have been used in the textile, cosmetic, pharmaceutical, and food industries. Such emulsions are often more stable than those produced conventionally and often require little, if any, surfactant. Emulsions with smaller droplet sizes within a narrow size distribution are obtained when compared to other methods. 

Emulsions are used extensively in the food, pharmaceutical, and cosmetics industries, where their most important properties include stability (both physical and qualitative), rheology, reactivity, shelf life, texture, appearance, and flavor. All of these properties are affected by droplet size and/or size distribution [107,108], which in turn are functions of the method of production. Because emulsions are thermodynamically unstable, they require energy input for production and usually rely on a stabilizing agent (emulsifier, surfactant) to remain stable over long periods [109]. 

Many products in the chemical and agrochemical, cosmetic, pharmaceutical, and food industries are emulsion-based. Their internal structure is composed of one or more fluids, with one being flnely dispersed as droplets within the other one. The size distribution of the droplets mainly influences characteristic product properties as color, texture, flow- and spreadability, viscosity, mouth-feel, shelf-life stability, and release of active ingredients. It therefore has to be maintained for the life-time of a product. Due to the extremely high interfacial area in these systems, this microstructure is thermodynamically unstable. By applying emulsiflers and thickeners, emulsions are kinetically stabilized for a certain amount of time. Elowever, shelf-life stability always is a big chal-... 

Since the initial introduction of laser diffraction instrumentation in the 1970s, many different applications to particle size analysis have been reported. These have included measurements of size distributions of radioactive tracer particles, ink particles used in photocopy machines, ziiconia fibers, alumina particles, droplets from electronic fuel injectors, crystal growth particles, coal powders, cosmetics, soils, resins, pharmaceuticals, metal catalysts, electronic materials, photographic emulsions, organic pigments, and ceramics. About a dozen instrument companies now produce LALLS instruments. Some LALLS instruments have become popular as detectors for size-exclusion chromatography. 

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