Multiple emulsions types

Most, if not all, milks contain sufficient amounts of lipase to cause rancidity. However, in practice, lipolysis does not occur in milk because the substrate (triglycerides) and enzymes are well partitioned and a multiplicity of factors affect enzyme activity. Unlike most enzymatic reactions, lipolysis takes place at an oil-water interface. This rather unique situation gives rise to variables not ordinarily encountered in enzyme reactions. Factors such as the amount of surface area available, the permeability of the emulsion, the type of glyceride employed, the physical state of the substrate (complete solid, complete liquid, or liquid-solid), and the degree of agitation of the reaction medium must be taken into account for the results to be meaningful. Other variables common to all enzymatic reactions—such as pH, temperature, the presence of inhibitors and activators, the concentration of the enzyme and substrate, light, and the duration of the incubation period—will affect the activity and the subsequent interpretation of the results. 

This is another innovative emulsion technique proposed for the efficient encapsulation of hydrophilic drug compounds involves the formation of double emulsions (multiple emulsions). In this technique, an aqueous core solution (W,) is emulsified in a polymer-organic solvent solution (O) to form the primary W/0 emulsion, which is further emulsified in an external aqueous solution (Wn), giving rise to the double emulsion of Wi/O/Wu type. Evaporation or extraction of the organic solvent yields a solid microcapsule with an aqueous core. The organic phase in (O) acts as a barrier between the two aqueous compartments, W, and Wu, to prevent the diffusion of hydrophilic drug compounds out of the core toward the external aqueous solution. Figure 45.5 depicts the microencapsulation by the Wi/O/Wn emulsion technique. 

Practical situations are not always so simple, and one may encounter multiple emulsions such as double emulsions, that is, emulsions that are oil-in-water-in-oil (O/W/O) or water-in-oil-in-water (W/O/W). For example, O/W/O denotes a double emulsion containing oil droplets dispersed in aqueous droplets that are in turn dispersed in a continuous oil phase. The double emulsion droplets can be quite large (tens of micrometres) and can contain many tens of droplets of the ultimate internal phase. Developments in and applications of double emulsions have been reviewed by Garti and Bisperink [69]. There can even be more complex emulsion types [33]. Figure 1.2 shows an example of a crude oil W/O/W/O (water-in-oil-in-water-in-oil) emulsion. The type of emulsion that is formed depends on a number of factors. 

As mentioned earlier, emulsions do not always occur in the idealized form of drops of one phase dispersed in another. The occurrence of double and multiple emulsions, ofthe types O/W/O, W/O/W, O/W/O/W, and so on, has already been... 

Three types of multiple emulsions may be distinguished [16] (Figure 12.11). This classification is based on the predominance of the multiple emulsion droplet type. Using isopropyl myristate as the oil phase, 5% Span 80 to prepare the primary W/O emulsion, and various surfactants to prepare the secondary emulsion, three main types of multiple emulsions were observed [16] Type A droplets contained on a large internal droplet, similar to that observed by Matsumoto et al. [17]. This type was produced when polyoxyethylene oxide (4) lauryl ether (Brij 30) was used as secondary emulsifier at 2%. Type B droplets contained several small internal droplets. These were prepared using 2% polyoxyethylene (16.5) nonylphenyl ether (Triton X-165). Type C drops entrapped a large number of small internal droplets. These were prepared using a 3 1 Span 80-Tween 80 mixture. 

Formulation Surfactants are used for the formulation of many pharmaceutical formulations such as suspensions, emulsions, multiple emulsions, semisolid and gels for topical application. In all cases the surfactants must be approved by the Food and Drug Admins-tration (FDA) and this limits the choice in pharmaceutical applications. Several surfactant molecules have been approved by the FDA, both of the ionic and nonionic type. The latter are perhaps the most widely used molecules in pharmaceuticals, e.g., sorbitan esters (Spans) and their ethoxylated analogues (Tweens). Polymeric surfactants of the PEO-PPO-PEO block type or Poloxamers (ICl, U.K.) are also used in many formulations. Many pharmaceutical emulsions, e.g., lipid and anesthetic emulsions, are formulated using egg lecithin which has to be pure and free from any toxic impurities. 

Water-in-oil solubilized adjuvant formulations of vaccines containing Clostridium welchii type D toxoid as antigen were prepared first in 1968 and tested in laboratory animals by Coles et al [238]. The adjuvant action of oil-in-water emulsions, multiple emulsions and water in gelled oil emulsions is well known but these varied systems have the disadvantages of high viscosity which makes injection physically difficult. Lin [236] quotes an HLB of 9.7 as the optimum value for water solubilization in mineral oil. Coles et al [238] found a value of 10. While the addition of a small quantity of the lipophilic surfactant Arlacel 80 (sorbitan mono-oleate) to a system of Tween 81 (polyoxyethylene (5)-sorbiton mono-oleate) alio wed increasing amounts of water to be solubilized, when toxoid solution was substituted for water the Arlacel decreased the amount which could... 

Although all multiple emulsions contain a range of droplet types, the predominance of one type led the authors [150,151] to categorize the emulsions as types A, B or C. The characteristics of the inclusion in the dispersed phase of emulsions has also been considered by Kessler and York [152] who have found that the... 

A double (multiple or complex) emulsion is an emulsion in an emulsion (Garti, 1997). Two main types of double emulsions can be distinguished water-in-oil-in-water (W/O/W) and oil-in-water-in-oil (OAV/O). A W/OAV emulsion consists of water droplets dispersed within larger oil droplets, which are themselves dispersed in an aqueous continuous phase. In an OAV/O emulsion, larger water droplets enclosing smaller oil droplets are dispersed in a continuous oil phase. W/O/W emulsions are more common than O/W/O emulsions. Other types of double emulsions such as oil-in-water-in-water (Kim et al., 2006) and ethanol-in-oil-in-water (Nakajima et al., 2003), have also been prepared and investigated. 

Emulsions in which water is the internal dispersed phase are termed water-in-oil emulsions (W/O), whereas emulsions in which oil is the dispersed phase and water is the continuous phase are known as oil-in-water (0/W) emulsions. More complex systems, in which one emulsion is further dispersed into another continuous phase, are called double emulsions, multiple emulsions, or emulsified emulsions [13-21] (Eig. 1). Two main types of double emulsions have been carefully studied W/O/W and O/W/O double emulsions. The average inner droplet size of the W/O emulsion in the double emulsion is usually smaller than 0.5 xm that of the outer, external double emulsion is quite large and often exceeds 20 qm. 

The term multiple emulsion describes a w/o emulsion ia an o/w emulsion. Eor example, when a w/o emulsion is added to water, no dispersion is expected unless the aqueous phase is fortified with a suitable emulsifier. The resultiag dispersioa may thea be a blead of a w/o and an o/w emulsion, or it may be a multiple emulsion of the w/o/w type. In this latter case, the initial w/o emulsion becomes the internal phase of the final product. Generally, these preparations are not very stable unless they are produced under rigidly controlled conditions (32,39,40). 

Polymer Particle Balances (PEEK In the case of multiconponent emulsion polymerization, a multivariate distribution of pjarticle propierties in terms of multiple internal coordinates is required in this work, the polymer volume in the piarticle, v (continuous coordinate), and the number of active chains of any type, ni,n2,. .,r n (discrete coordinates), are considered. Therefore... 

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. 

Y. Kita, S. Matsumoto, and D. Yonezawa Permeation of Water Through the Oil Layer in W/O/W-Type Multiple-Phase Emulsions. Nippon Kagaku Kaishi 1, 11 (1978). 

Electrostatic and non-electrostatic biopolymer complexes can also be used as effective steric stabilizers of double (multiple) emulsions. In this type of emulsion, the droplets of one liquid are dispersed within larger droplets of a second immiscible liquid (the dispersion medium for the smaller droplets of the first liquid). In practice, it is found that the so-called direct water-in-oil-in-water (W/O/W) double emulsions are more common than inverse oil-in-water-in-oil (O/W/O) emulsions (Grigoriev and Miller, 2009). In a specific example, some W/O/W double emulsions with polyglycerol polyricinoleate (PGPR) as the primary emulsifier and WPI-polysaccharide complexes as the secondary emulsifying agent were found to be efficient storage carriers for sustained release of entrapped vitamin Bi (Benichou et al., 2002). 

Figure 7.24 Schematic presentation of a multiple (double) emulsion droplet of the most common water-in-oil-in-water type.

As mentioned earlier, emulsions do not always occur in the idealized form of drops of one phase dispersed in another. The occurrence of double and multiple emulsions, of the types O/W/O, W/O/W, O/W/O/W, etc., has already been mentioned (See Figure 1.2). In these cases the above techniques can sometimes be used to determine the continuous phase, but not always. For example, the dye test may produce misleading results when applied to a multiple emulsion, or to a bi-continu-ous emulsion. In particular, it is very difficult to follow the aggregation and/or coa-... 

A type of processing equipment in which the entire amount of material to be used is put into the mixer and mixed for a definite period, with multiple recirculation of material through the mixing zone, in contrast to what happens in a continuous mixer. After the mixing period the whole amount of material is removed from the mixer. In oil production or processing, the process in which emulsion is collected in a tank and then broken in a batch. This process is used as opposed to continuous or flow-line treating of emulsions. 

Emulsions and suspensions are colloidal dispersions of two or more immiscible phases in which one phase (disperse or internal phase) is dispersed as droplets or particles into another phase (continuous or dispersant phase). Therefore, various types of colloidal systems can be obtained. For example, oil/water and water /oil single emulsions can be prepared, as well as so-called multiple emulsions, which involve the preliminary emulsification of two phases (e.g., w/o or o/w), followed by secondary emulsification into a third phase leading to a three-phase mixture, such as w/o/w or o/w/o. Suspensions where a solid phase is dispersed into a liquid phase can also be obtained. In this case, solid particles can be (i) microspheres, for example, spherical particles composed of various natural and synthetic materials with diameters in the micrometer range solid lipid microspheres, albumin microspheres, polymer microspheres and (ii) capsules, for example, small, coated particles loaded with a solid, a liquid, a solid-liquid dispersion or solid-gas dispersion. Aerosols, where the internal phase is constituted by a solid or a liquid phase dispersed in air as a continuous phase, represent another type of colloidal system. 

Besides W/O and O/W emulsions there are so-called multiple emulsions of the W/O/W type. These emulsions can be produced in a one-stage modified PIT process [32] or by emulsification of a primary W/O emulsion in an outer water phase. These systems are an approach to protect sensitive active substances such as vitamins or enzymes in a formulation. 

No systematic studies of the use of silicone surfactants as emulsifiers have yet been published. Silicone polyoxyalkylene copolymers with relatively high molecular weight and a high proportion of silicone are effective water-in-silicone oil emulsifiers and a recent study of these copolymers suggests that they stabilize emulsions by a solid-particle mechanism [68]. This type of silicone surfactant has been used to prepare transparent water-in-oil emulsions (often with an active ingredient in the internal phase) for use as deodorants or antiperspirants as well as cosmetics and other personal care products. Their use as drug delivery vehicles has also been claimed. These copolymers can also be used to prepare multiple emulsions not requiring a two-pot process. 

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