Yield, multiple emulsions

By first dispersing the EUP in water containing the base for neutralization of the carboxyl acid groups of the EUP and then adding the comonomer with intensive stirring, normal emulsions are obtained. They are favorable because, with multiple emulsions, insoluble polymers are formed, which decrease the yield of microgels. 

The yield of the multiple emulsion can be determined using dialysis for W/O/W multiple emulsions. A water-soluble marker is used and its concentration in the outside phase is determined. 

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. 

Abnormal regions C and B also exhibit low-stability emulsions, a feature that is consistent with the fact that the emulsion type, and thus the interface curvature, is opposite to the one favored by the fomtulation effect. Since multiple emulsions are often made in these regions, a closer look is warranted. For instance, a multiple Wi/O/Wi emulsion i.s found in the C" region. W represents the most internal phase, i.e.. the water dnqtlcts that are located inside the oil drops. It may be considered that the principal" or outside" 0/W2 emulsion has the W,/0 inside" emulsion as internal phase. Since the W,/0 inside emulsion matches the expected type from formulation effects, it is certainly stable, whereas the outside emulsion is not. Thus, such a W,/0/W emulsion would quickly decay in a two-layer system, consisting of a W. phase and an oil layer that would actually be a W /0 emulsion, which is expected to be quite stable if the formulation is sufficiently away from optimum. This means that such unstable" multiple emulsions do not necessarily yield a quick and complete phase separation unless the formulation is q>propriate. e.g.. near-optimum. This feature could be useful for applications dealing with controlled release or capture through mass transfer. 

We end this section by summarizing the areas where we feel that the NMR diffusion method will prove important in future studies of emulsions and refer to a more detailed account presented in Chapter 10 of this book. As theories describing emulsion stability become more refined, there will be a need for data on droplet size distribution and also on total emulsion droplet area and how these quantities evolve with time. As outlined above, NMR is eapable of providing sueh data. Another important question pertains to the mi-crostrueture of the continuous phase, which can be studied both in the emulsion phase and also in the phase-separated systems which yield the emulsion. Finally, we note that one important class of emulsions, namely, multiple emulsions, is practically virgin territory with regard to NMR studies. In the characterization and understanding of important features of these systems NMR will most likely play an important role. 

Dialysis As mentioned above, this could be used to measure the yield of the multiple emulsion it can also be applied to follow any solute transfer from the inner droplets to the outer continuous phase. 

Magdassi S, Frenkel M, Garti N. 1984. On the factors affecting the yield of preparation and stability of multiple emulsions. / Disper Sci Tech 5(1) 49-59. 

Mohamed SM, Ghazy FS, Mahdy MA, Gad MA. 1989. Factors affecting the yield of multiple emulsion and drug release. Mans / Pharm Sci 5 56-71. 

Koberstein-Hajda and Dickinson (1996) incorporated unmodified faba protein into the inner aqueous phase using sorbitan monooleate (Span 80) as a hydrophobic emulsifier and sodium caseinate as a hydrophilic emulsifier. The authors concluded that encapsulation of the inner phase with caseinate and a small quantity of Span 80 did not improve stability of the multiple emulsion, while increasing the protein and the Span 80 content improved both yield and stability. 

Gelation of the Outer Aqueous Phase (W/O/Gel) Most of the additives inserted in the multiple emulsions under study are not permitted in foods. Viscosities were found to be enhanced by cellulose derivatives such as hydro-xypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), hydro-xyethyl cellulose (HEC), and the natural hydrocolloids, such as xanthan, guar gum, and carrageenan. The viscosity or gelling agents can affect some of the multiple emulsion properties such as entrapping yields, stability, droplet size, consistency, and skin feel (Ozer et al., 2000). 

Emulsions prepared with linear alkanes, n-decane, n-dodecane, and n-tet-radecane yielded stable multiple emulsions with a stability index for 28 days (ESl2s) in the 0.85 to 1.10 range at 25°C. Creaming (sedimentation) was quickly detected (2 hours) at all tested storage temperatures (4°C, 25°C, and 40°C). When the external oil phase (O2) consisted of silicone oils, flumethrin releases were significantly slowed and the drug concentration in the external oil phase remained at very low levels (below 2000 ppm) after 28 days of storage at 25°C. 

The concept of stabilizing emulsions by solid particles (mechanical stabilization) was described (Oza and Frank, 1986) tor colloidal microcrystalline cellulose (CMCC) that is adsorbed in a solid form onto oil droplets at the interface of a W/O emulsion with improved stability. Khopade and Jain repeated use of a similar process and managed to stabilize W/OAV emulsions by using MCC (microcrystalline colloidal cellulose) particles at both interfaces (Khopade and Jain, 1998). The droplets were small, and the yield of the multiple emulsion was fairly good. The increasing concentration of MCC in either internal or external phase increased droplet sizes. These systems showed promise in tuberculosis therapy. 

At a gum concentration of 0.5 wt% the protein concentration does not affect the rheological behavior of the multiple emulsion that conserves its elasticity properties at all ratios with phase angle (8) values around 25° at all proteins contents. At the same time the yield of preparation of multiple emul-... 

Spherical silica particles containing retinol have been fabricated using O/ W/O multiple emulsion and the sol-gel method (Lee et al., 2001). O/W/O multiple emulsions were stabilized with hydroxypropyl cellulose (HPC) and surfactants such as Tween 20 and Span 80. In addition a polymeric stabilizer present in the intermediate aqueous phase was shown to improve the encapsulation efficiency. In the presence of polyvinyl alcohol the yield of encapsulation efficiency of retinol was 7%. With Pluronic P123 (a block copolymer of ethylene oxide propylene oxide) a yield of encapsulation of 31% could be reached. Figure 7.24 shows the retinol released profile from silica particles prepared in the O/W/O multiple emulsions and stabilized with different surfactant and different polymeric stabilizers in the intermediate aqueous phase. 

The sol-gel reaction during the formation of silica particles in the multiple emulsion system started in the external oil phase containing the precursor alkoxide type (tetraethyl orthosilicate, TEOS), as shown in Figure 7.25. Under stirring, the TEOS molecules can penetrate the surfactant layer surrounding the aqueous phase, and then hydrolysis can start. As hydrolysis proceeds, the Si-OH based molecules diffuse and dissolve in the aqueous phase. A gel network is formed by condensation, yielding the insoluble hydrated silica encapsulating the retinol molecules. The water content in the multiple emulsion was demonstrated to impart the final shape and size distribution of the particles. 

So multiple emulsions present interesting advantages (1) an easy fabrication process at room temperature with a higher entrapment yield and (2) a higher fraction released at skin temperature compared with the results obtained at room temperature. Two types of thermothickening polymers were studied ... 

Methotrexate loaded multiple emulsion was prepared by using bovine serum albumin as stabilizer in internal phase to avoid internal droplet coalescence. By microwave technique the albumin in internal aqueous phase was sohdified to form a microspheres-in-oil-in-water emulsion (S/O/W). The formulation and process variables were optimized and evaluated for physicochemical characteristics, such as microscopic structure, electrical charge, particle size distribution, rheological behavior, yield, entrapment efficiency, drug release and stability. The emulsions were found to be stable and showed prolonged release in vitro (Tao et al., 1992). 

Cosurfactant facilitates droplet size reduction in the fME range. The multiple emulsion was diluted with equal volume of ice-cold external phase (<4°C), stirred for 15 minutes, and immediately transferred to a refrigerator. The pH of the external phase was increased to about 8.0 to 8.9 and then restored to 7.4 with addition of an acid. The multiple emulsion was formed with a relatively high percentage of the secondary surfactant further a cosurfactant had to be added to reduce the size of multiple emulsion. The formulation and process variables Uke amount of surfactants, phase volume, and time period of sonication for both emulsification steps were optimized by way of the appropriate evaluation parameters, mainly solidification, droplet size, yield, viscosity, and/or stability. 

Another approach is to assemble multiple chelates either covalently (11) (oligomer, polymer, and dendrimer) or non-covalently (12, 13) (micelle, liposome, and emulsion). These approaches all yield higher molecular relaxivities because of the assembly, but the per-ion relaxivity also is increased because motion is slowed. Fast internal motions can limit these relaxivity gains, but this limitation can be overcome by rigidifying the structure in some way (14). 

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