Emulsions dispersed systems

Nonionic surfactants and both natural and synthetic polymers (which are collectively referred to as polymeric surfactants), when used to stabilise soHd/hquid (suspensions) andliquid/liquid (emulsions) disperse systems, play important roles in many industrial applications including paints, cosmetics, agrochemicals, and ceramics. Nonionic surfactants and polymers are particularly important for the preparation of concentrated dispersions - that is, with a high volume fraction

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Ttp 6 (related to Ttp 5) Impurities, transfer to monomer, and terminal double bonds. The role of impurities should not be neglected, especially in emulsion/dispersion systems. See the case smdies described in Penlidis et al. [31], Chien and Penlidis [32], and Dub6 and Penlidis [33], for both homopolymerization and multicomponent polymerization systems, in both bulk/solution and emulsion. Transfer to... 

Product Concentrate. An aerosol s product concentrate contains the active ingredient and any solvent or filler necessary. Various propellent and valve systems, which must consider the solvency and viscosity of the concentrate—propellent blend, may be used to deUver the product from the aerosol container. Systems can be formulated as solutions, emulsions, dispersions, or pastes. 

Dispersed Systems. Many fluids of commercial and biological importance are dispersed systems, such as soflds suspended in Hquids (dispersions) and Hquid-Hquid suspensions (emulsions). Examples of the former include inks, paints, pigment slurries, and concrete examples of the latter include mayonnaise, butter, margarine, oil-and-vinegar salad dressing, and milk. Blood seems to fall in between as it is a suspension of deformable but not hquid particles, and it does not behave like either a dispersion or an emulsion (69) it thus has an interesting rheology (70). 

A classification of dispersed systems on this basis has been worked out by Pawlow (30) (1910), who introduces a new variable called the concentration of the dispersed phase, i.e., the ratio of the masses of the two constituents of an emulsion, etc. When the dispersed phase is finely divided the thermodynamic potential is a homogeneous function of zero degree in respect of this concentration. 

This chapter describes the basic principles involved in the development of disperse systems. Emphasis is laid on systems that are of particular pharmaceutical interest, namely, suspensions, emulsions, and colloids. Theoretical concepts, preparation techniques, and methods used to characterize and stabilize disperse systems are presented. The term particle is used in its broadest sense, including gases, liquids, solids, molecules, and aggregates. The reader may find it useful to read this chapter in conjuction with Chapters 8, 12, and 14, since they include some of the most important applications of disperse systems as pharmaceutical dosage forms [1]. 

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. 

The defined size ranges and limits are somewhat arbitrary since there are no specific boundaries between the categories. The transition of size ranges, either from molecular dispersions to colloids or from colloids to coarse dispersions, is very gradual. For example, an emulsion may exhibit colloidal properties, and yet the average droplet size may be larger than 1 pm. This is due to the fact that most disperse systems are heterogeneous with respect to their particle size [1-2]. 

The number of the constituent phases of a disperse system can be higher than two. Many commercial multiphase pharmaceutical products cannot be categorized easily and should be classified as complex disperse systems. Examples include various types of multiple emulsions and suspensions in which solid particles are dispersed within an emulsion base. These complexities influence the physicochemical properties of the system, which, in turn, determine the overall characteristics of the dosage forms with which the formulators are concerned. 

Content uniformity and long-term stability of a pharmaceutical product are required for a consistent and accurate dosing. Aggregation of dispersed particles and resulting instabilities such as flocculation, sedimentation (in suspensions), or creaming and coalescence (in emulsions) often represent major problems in formulating pharmaceutical disperse systems. 

The preparation of satisfactory disperse systems consists of three main steps preparing the internal phase in the proper size range, dispersing the internal phase in the dispersion medium, and, finally, stabilizing the resultant product. These three steps may be done sequentially, but in many cases (e.g., emulsions), they are usually done simultaneously. 

B Idson. Pharmaceutical emulsions. In HA Lieberman, MM Rieger, GS Banker, eds. Pharmaceutical Dosage Forms Disperse Systems, Vol. 1. New York Marcel Dekker, 1988, pp 199-244. 

An emulsion is a dispersed system of two immiscible phases. Emulsions are present in several food systems. In general, the disperse phase in an emulsion is normally in globules 0.1-10 microns in diameter. Emulsions are commonly classed as either oil in water (O/W) or water in oil (W/O). In sugar confectionery, O/W emulsions are most usually encountered, or perhaps more accurately, oil in sugar syrup. One of the most important properties of an emulsion is its stability, normally referred to as its emulsion stability. Emulsions normally break by one of three processes creaming (or sedimentation), flocculation or droplet coalescence. Creaming and sedimentation originate in density differences between the two phases. Emulsions often break by a mixture of the processes. The time it takes for an emulsion to break can vary from seconds to years. Emulsions are not normally inherently stable since they are not a thermodynamic state of matter. A stable emulsion normally needs some material to make the emulsion stable. Food law complicates this issue since various substances are listed as emulsifiers and stabilisers. Unfortunately, some natural substances that are extremely effective as emulsifiers in practice are not emulsifiers in law. An examination of those materials that do stabilise emulsions allows them to be classified as follows ... 

Emulsion It may be defined as- a dispersed system containing at least two immiscible liquid phases . 

Sustained release from disperse systems such as emulsions and suspensions can be achieved by the adsorption of appropriate mesogenic molecules at the interface. The drug substance, which forms the inner phase or is included in the dispersed phase, cannot pass the liquid ciystals at the interface easily and thus diffuses slowly into the continuous phase and from there into the organism via the site of application. This sustained drug release is especially pronounced in the case of multilamellar liquid crystals at the interface. 

The physical picture of emulsion polymerization is based on the original qualitative picture of Harkins [1947] and the quantitative treatment of Smith and Ewart [1948] with subsequent contributions by other workers [Blackley, 1975 Casey et al., 1990 Gao and Penlidis, 2002 Gardon, 1977 Gilbert, 1995, 2003 Hawkett et al., 1977 Piirma, 1982 Poehlein, 1986 Ugelstad and Hansen, 1976]. Table 4-1 shows a typical recipe for an emulsion polymerization [Vandenberg and Hulse, 1948]. This formulation, one of the early ones employed for the production of styrene-1,3-butadiene rubber (trade name GR-S), is typical of all emulsion polymerization systems. The main components are the monomer(s), dispersing medium, emulsifier, and water-soluble initiator. The dispersing medium is the liquid, usually water,... 

The largest portion of the monomer (>95%) is dispersed as monomer droplets whose size depends on the stirring rate. The monomer droplets are stabilized by surfactant molecules absorbed on their surfaces. Monomer droplets have diameters in the range 1-100 pm (103-105 nm). Thus, in a typical emulsion polymerization system, the monomer droplets are much larger than the monomer-containing micelles. Consequently, while the concentration of micelles is 1019-1021 the concentration of monomer droplets is at most 1012-1014 L 1. A further difference between micelles and monomer droplets is that the total surface area of the micelles is larger than that of the droplets by more than two orders of magnitude. The size, shape, and concentration of each of the various types of particles in the... 

In a dispersed system, it is possible to have both phases in existence at the same time. However, whenever fuels emulsify with water, water-in-oil emulsion typically forms. Agents which comprise the external phase of an emulsion are usually the most soluble in the bulk liquid in which the emulsion exists. 

Mixing processes involved in the manufacture of disperse systems, whether suspensions or emulsions, are far more problematic than those employed in the blending of low-viscosity miscible liquids due to the multi-phasic character of the systems and deviations from Newtonian flow behavior. It is not uncommon for both laminar and turbulent flow to occur simultaneously in different regions of the system. In some regions, the flow regime may be in transition, i.e., neither laminar nor turbulent but somewhere in between. The implications of these flow regime variations for scale-up are considerable. Nonetheless, it should be noted that the mixing process is only completed when Brownian motion occurs sufficiently to achieve uniformity on a molecular scale. 

Liquid dosage forms which are disperse systems (colloidal, i.e., microspheres, nanoparticles, and micelles suspensions and emulsions) often contain preservatives which are methyl, ethyl, propyl, and butyl esters of para-hydroxybenzoic acid in various combinations. A typical example is the antacid suspensions which have high pH values which make the esters of the preservatives susceptible to hydrolysis. One way to circumvent this problem is to use several preservatives in combination with the hope that some quantities of the preservatives will remain to prevent the suspension from microbial attack. A report showing the assay of the four esters and the parent acid (one of the decomposition products) in drug products in which all the preservatives were used has been given [13]. 

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