Phase volumes emulsions

Once good physical stability of an emulsion is insured, its commercialization mandates chemical stability of the incorporated drug and other essential components for at least 18 months. Key factors that affect the chemical stability of pharmaceutical emulsions include drug stability in oil, drug stability in aqueous media, drug concentration in oil and emulsion, phase volume ratio, droplet size, presence of excipients, and presence of air and/or peroxide radicals. As mentioned earlier, choice of appropriate antioxidant is important. 

Emulsions are characterized in terms of dispersed / continuous phase, phase volume ratio, droplet size distribution, viscosity, and stability. The dispersed phase is present in the form of microscopic droplets which are surrounded by the continuous phase both water-in-oil (w/o) and oil-inwater (o/w) emulsions can be formed. The typical size range for dispersed droplets which are classified as emulsions is from 0.25 to 25 p (6). Particles larger than 25 p indicate incomplete emulsification and/or impending breakage of the emulsion. Phase volume ratio is the volume fraction of the emulsion occupied by the internal (dispersed) phase, expressed as a percent or decimal number. Emulsion viscosity is determined by the viscosity of the continuous phase (solvent and surfactants), the phase volume ratio, and the particle size (6). Stroeve and Varanasi (7) have shown that emulsion viscosity is a critical factor in LM stability. Stability of... 

The fluidization quality significantly decreased when the reaction involving a decrease in the gas volume was carried out in a fluidized catalyst bed. In the present study, we carried out the hydrogenation of CO2 and used relatively large particles as the catalysts. Since the emulsion phase of the fluidized bed with these particles does not expand, we expected that the bed was not affected by the gas-volume decrease. However, we found that the fluidization quality decreased and the defluidization occurred. We studied the effects of the reduction rate of the gas volume and the maximum gas contraction ratio on the fluidization behavior. 

In the case of a FCB, the gas volume decreases when the reaction involving a decrease in the volume is carried out at constant temperature and under constant pressure. If the gas in the emulsion phase cannot be compensated by the gas supply from bubbles, the emulsion phase is condensed and bubbles cannot rise through the emulsion phase. Finally, defluidization in the bed occurs. This part of the packed bed will be lifted up like a moving piston. 

In the case of a FCB with small particles, the emulsion phase expands [5, 6, 7] when the bed is fluidized. This would make the bed sensitive to the decrease in the gas volume in the emulsion phase. If this assumption is true, we can postulate that the fluidization quality is hardly affected by the gas-volume reduction when the particles, which induce a small emulsion phase expansion, are used. The emulsion phase expansion decreases with increasing particle size and density [6]. In the present study, therefore, the particles used were larger and heavier than that generally used in the FCB. We carried out the hydrogenation of CO2 in a... 

The Davidson and Harrison (1963) model assumed there was no net exchange of gas between the bubble and the emulsion phase. The validity of this assumption was later questioned by Botterill et al. (1966), Rowe and Matsuno (1971), Nguyen and Leung (1972), and Barreto et al. (1983). The predicted bubble volume, if assumed no net gas exchange, was considerably larger than the actual bubble volume experimentally observed. 

The first criterion for the formation of a HIPE is, of course, the presence of two immiscible liquids, one of which is water (or aqueous solution), almost without exception. The nature of the organic, or oil, phase can vary to a considerable extent, although the most stable HIPEs are generally produced with more hydrophobic liquids. However, it is the nature of the surfactant employed to stabilise the HIPE which will ultimately facilitates its formation. Above a certain critical limit of internal phase volume, an emulsion will tend to invert to the opposite type, i.e. an oil-in-water (o/w) emulsion will become the w/o variety, and vice versa. This can be prevented from occurring by careful choice of surfactant, such that it is completely insoluble in the dispersed phase of the emulsion. 

Bibette has used this method to study the effect of osmotic pressure on the stability of thin films in concentrated o/w emulsions [96], by means of an osmotic stress technique. The emulsion is contained in a dialysis bag, which is immersed in an aqueous solution of surfactant and dextran, a water-soluble polymer. The bag is permeable to water and surfactant, but impermeable to oil and polymer. The presence of the polymer causes water to be drawn out of the emulsion, increasing the phase volume ratio and the deformation of the dispersed droplets (Fig. 10). 

A considerable amount of experimental work has been carried out on the so-called gel emulsions of water/nonionic surfactant/oil systems [9-14, 80, 106, 107]. These form in either the water-rich or oil-rich regions of the ternary phase diagrams, depending on the surfactant and system temperature. The latter parameter is important as a result of the property of nonionic surfactants known as the HLB temperature, or phase inversion temperature (PIT). Below the PIT, nonionic surfactants are water-soluble (hydrophilic form o/w emulsions) whereas above the PIT they are oil-soluble (hydrophobic form w/o emulsions). The systems studied were all of very high phase volume fraction, and were stabilised by nonionic polyether surfactants. 

Another process which leads to HIPE instability is gravitational syneresis, or creaming, where the continuous phase drains from the thin films as a result of density differences between the phases. This produces a separated layer of bulk continuous phase and a more concentrated emulsion phase. The separated liquid can be located either above or below the emulsion, depending on whether the continuous phase is more or less dense, respectively, than the dispersed phase. This process has been studied by Princen [111] who suggests that it can be reduced by a number of parameters, including a high internal phase volume, small droplet sizes, a high interfacial tension and a small density difference between phases. 

The non-aqueous HIPEs showed similar properties to their water-containing counterparts. Examination by optical microscopy revealed a polyhedral, poly-disperse microstructure. Rheological experiments indicated typical shear rate vs. shear stress behaviour for a pseudo-plastic material, with a yield stress in evidence. The yield value was seen to increase sharply with increasing dispersed phase volume fraction, above about 96%. Finally, addition of water to the continuous phase was studied. This caused a decrease in the rate of decay of the emulsion yield stress over a period of time, and an increase in stability. The added water increased the strength of the interfacial film, providing a more efficient barrier to coalescence. 

Williams et al. have also investigated the effect of variation of the DVB content of the monomer phase on the cellular structure of the resulting foam [130]. The phase volume and surfactant and initiator concentrations were kept constant while the DVB content was increased from 0 to 100% this caused a drop in average cell size from 15 pm to 6 pm. The increased hydrophobicity of DVB compared to styrene probably results in a more stable emulsion, giving a slower rate of droplet coalescence and smaller average cell size. 

The idea of the preparation of porous polymers from high internal phase emulsions had been reported prior to the publication of the PolyHIPE patent [128]. About twenty years previously, Bartl and von Bonin [148,149] described the polymerisation of water-insoluble vinyl monomers, such as styrene and methyl methacrylate, in w/o HIPEs, stabilised by styrene-ethyleneoxide graft copolymers. In this way, HIPEs of approximately 85% internal phase volume could be prepared. On polymerisation, solid, closed-cell monolithic polymers were obtained. Similarly, Riess and coworkers [150] had described the preparation of closed-cell porous polystyrene from HIPEs of water in styrene, stabilised by poly(styrene-ethyleneoxide) block copolymer surfactants, with internal phase volumes of up to 80%. 

Applying the appropriate material balances for the solids and the gas, the fraction of the bed occupied by the bubbles and wakes can be estimated using the Kunii-Levenspiel model. The fraction of the bed occupied by that part of the bubbles which does not include the wake, is represented by the parameter d, whereas the volume of the wake per volume of the bubble is represented by a. Consequently, the bed fraction in the wakes is a and the bed fraction in the emulsion phase (which includes the clouds) is 1 — <5 — ot<5. Then (Fogler, 1999)... 

The complete mixing of solids in the emulsion phase is necessary for considering the various parameters, involving the mass or volume of solids constant, throughout the reactor. That is exactly the case in the two-phase model and the Levenspiel-Kunii three-phase model. This is achieved by circulation of the solids through their entrainment by bubbles, as shown in Figure 3.61. As solids fall from the upper portions of the bed, they follow... 

Lbe = the mass transfer coefficient between the bubble and emulsion phase (m3 gas interchange volume/m3 of reactor) (1/s) yb = the volume fraction of the bubble occupied by solids ( rh,vs) = the reaction rate in bubbles per unit volume of solids, based on the reactant... 

Figure 3.63 Volume fractions in a two-phase fluidized bed (where e denotes the emulsion phase).

Accelerated stability tests using the emulsion volume index (EVI) Accelerated aging procedure in which an emulsion in a microhematocrit tube is subjected to centrifugal force EVI = (length of emulsion phase/lolul length of column) (% fal/0.9) x 100. A higher EVI indicates a more stable emulsion under the conditions of the test. 

Calculate the dispersed-phase volume fraction (())) of the emulsion using the equation... 

Figure 13. Ultrasonic determination of creaming profiles. is the disperse phase volume fraction, t is the time and x is the height of the emulsion.

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