Multiple emulsification method

Figure 16.2 Schematic representation of two preparation methods for water-in-oil (W/O) highly concentrated emulsions (a) Slow addition of dispersed phase to the continuous phase (conventional method) (b) weighting and shaking all components together (multiple emulsification method).

Multiple emulsions of the oil-in-water-in-oil type, where both the inner and the external oil phases were medium chain triglyceride (MCT), were prepared by the two-step emulsification method. The emulsifying agent at the inner oil-water interface was a combination of WPI-xanthan gum hybrid at different ratios and 3wt% Abil EM90 (a hydrophobic polyether-polysiloxane block copolymer) as the external emulsiher. Typical multiple emulsion composition is described in Table 7.2 and release profiles of flumethrin (a veterinary drug model) at 25°C are presented in Figure 7.15. 

The next chapter by G. T. Vladisavljevic and R. A. Williams is a comprehensive and systematic review of new techniques of preparation of multiple emulsions, emulsions, and microparticles. The authors envisage the ways to form multiple droplets by using membrane emulsification processes and microchan-nel and microcapUlary devices. They also pay special attention to the preparation of solid microparticles via a double emulsion emulsification method using membrane emulsification and microfiuidic devices. 

In the next chapter, T. Hino and T. Ohwaki use a two-step pumping emulsification method to prepare lipiodol W/O/W multiple emulsions for transcatheter arterial embolization therapy. 

Figure 11.12 Steps in the emulsification process by the multiple emulsion method...

One of the major drawbacks of liposomes is related to their preparation methods [3,4]. Liposomes for topical delivery are prepared by the same classic methods widely described in the literature for preparation of these vesicles. The majority of the liposome preparation methods are complicated multistep processes. These methods include hydration of a dry lipid film, emulsification, reverse phase evaporation, freeze thaw processes, and solvent injection. Liposome preparation is followed by homogenization and separation of unentrapped drug by centrifugation, gel filtration, or dialysis. These techniques suffer from one or more drawbacks such as the use of solvents (sometimes pharmaceutically unacceptable), an additional sizing process to control the size distribution of final products (sonication, extrusion), multiple-step entrapment procedure for preparing drug-containing liposomes, and the need for special equipment. 

Membrane emulsification is an appropriate technology for production of single and multiple emulsions and suspension. It was proposed for the first time at the 1988 Autumn Conference ofthe Society of Chemical Engineering, Japan. Since then, the method has continued to attract attention in particular in Japan, but also in Europe [1-10]. 

Liu, R., Ma, G.H., Meng, F.-T., and Su, Z.-G., Preparation of uniform-sized PLA microcapsules by combining Shirasu Porous Glass membrane emulsification technique and multiple emulsion-solvent evaporation method, J. Contrail. Ret, 103, 31, 2005. 

A technique based on the formation of a multiple emulsion with an external aqueous phase was developed for the encapsulation of water-soluble drugs in order to replace the external oil phase. Possible unwanted interactions between the oil and the emulsified wax such as swelling or dissolution of the wax, clean-up requirements of the final product, and recovery of the oil phase could be eliminated. In analogy to the encapsulation of water-soluble drugs within polymeric microparticles by a w/o/w-solvent evaporation method, a molten wax phase was used instead of an organic polmer solution. A heated aqueous solution of pseudoephedrine HCl was emulsified into the molten carnauba wax, followed by the emulsification of this w/o-emulsion into a heated external aqueous phase. The temperature of the internal and external aqueous phases had to be kept above the melting temperature of the wax in order to avoid premature... 

The microchannel emulsion technique has been extended to the formation of multiple emulsions [158-163], encapsulation [123, 158, 164—166], polymer bead formation [123, 125, 167-169], demulsification [116, 158, 170], and even microbubble formation [171]. New methods of stabilizing emulsions have also been investigated in this realm, including particle-stabilized [172] and protein-stabilized emulsions [173], with some work in emulsification without surfactants [135,146]. In the case of multiple emulsions, microchannel architecture can enable the formation of W/O/W emulsions in which two water droplets of different compositions can be encased in the same oil droplet [163]. 

Some preparation methods specific to the formation of nanoparticle suspensions are provided in References [20,62,63]. Many such methods are simply conventional colloidal suspension preparation methods that have been extended to produce smaller particle sizes, but others involve novel approaches. Some ofthese involve making nanoemulsions as a first step. For example, membrane, microfluidic and nanofluidic devices have been used to make nanoscale emulsions of all kinds, as already noted earlier, and the emulsion droplets so generated can be used in turn to make sohd microparticles and nanoparticles. If the nanoparticles are intended to encapsulate other materials, then a double emulsification technique can be used, at elevated temperature, to prepare a multiple emulsion (i.e. 

Higashi et al. (22), described a new method of producing W/O/W multiple emulsions by a membrane emulsification technique. This method permits the formation of monodis-persed liquid microdroplets containing aqueous micro-... 

Double emulsions (or in more general terms, multiple emulsions) are droplets of one kind of fluid that are encapsulated inside drops of a second fluid (or themselves can be encapsulated inside droplets of yet another fluid). Conventionally, double emulsions are produced using shear cells or porous membrane plates however, the distributions of sizes of primary droplets and double emulsion droplets are poorly controlled. For multiple emulsions (triple emulsions or droplets), the polydispersity makes the methods impractical. Microfluidic sequential emulsification offers the ability to produce double (and multiple) emulsions with narrow polydispersity and controlled structure [59,60]. 

Grossiord et al. discuss similar method based on emulsified microemul-sions. The idea is to disperse an oil phase within water by surfactant and to form L2 phase (water-in-oil microemulsion) (Grossiord et al., 1998). This phase is further emulsified with water to form multiple emulsion (Figure 7.3). The problem is that there is no evidence of the formation of multiple emulsions and that the internal phase remains, after the second emulsification process, a L2 phase of a submicronal droplets in size with intrinsic thermodynamic stability. 

Other methods to prepare multiple emulsions that were envisaged include the membrane emulsification technique (Higashi et al., 1995). In this method the primary OAV or W/O emulsion is formed by sonication and then filled into the upper chamber of a special apparatus (Figure 7.6). The external phase of the final multiple emulsion is continuously injected into the lower chamber... 

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