Scale dispersed systems

LH Block. Scale-up of disperse systems Theoretical and practical aspects. In HA Lieberman, MM Rieger, GS Banker, eds. Pharmaceutical Dosage Forms Disperse Systems, Vol. 3, 2nd ed. New York Marcel Dekker, 1998, pp 363-394. 

A turbine type agitator is commonly used for liquid-solid systems. Mixing rates depend on the forces required to suspend all solid particles. Minimum levels can be determined for (1) lifting the particles, and (2) for suspending them in an homogeneous manner [200]. Similar requirements apply to liquid-liquid systems. For cases where two poorly miscible fluids of about equal volume are used in the reaction, the mixer is placed at the interface. For a bench-scale experimental system of about 2 liters capacity, the minimum rotational speed to obtain well-dispersed system is 300 to 400 rpm [201], depending on the type of mixer. This rotational value decreases as the vessel volume increases. 

Fig. 7.1 Scanning electron micrographs of a typical carbon dispersion from glucose as a model system (scale bar 2 pm).

Particles produced in the gas phase must be trapped in condensed media, such as on solid substrates or in liquids, in order to accumulate, stock, and handle them. The surface of newly formed metallic fine particles is very active and is impossible to keep clean in an ambient condition, including gold. The surface must be stabilized by virtue of appropriate surface stabilizers or passivated with controlled surface chemical reaction or protected by inert materials. Low-temperature technique is also applied to depress surface activity. Many nanoparticles are stabilized in a solid matrix such as an inert gas at cryogenic temperature. At the laboratory scale, there are many reports on physical properties of nanometer-sized metallic particles measured at low temperature. However, we have difficulty in handling particles if they are in a solid matrix or on a solid substrate, especially at cryogenic temperature. On the other hand, a dispersion system in fluids is good for handling, characterization, and advanced treatment of particles if the particles are stabilized. 

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. 

Insofar as the scale-up of pharmaceutical liquids (especially disperse systems) and semisolids is concerned, virtually no guidelines or models for scale-up have generally been available that have stood the test of time. Uhl and Von Essen (55), referring to the variety of rules of thumb, calculation methods, and extrapolation procedures in the literature, state, Unfortunately, the prodigious literature and attributions to the subject [of scale-up] seemed to have served more to confound. Some allusions are specious, most rules are extremely limited in application, examples give too little data and... 

As Tatterson (57) notes, there is much more volume on scale-up than is typically recognized. This is one feature of scale-up that causes more difficulty than anything else. For disperse systems, a further mechanistic... 

Block LH. Scale-up of disperse systems theoretical and practical aspects. In Lieberman HA, Rieger MM, Banker GS, eds. Pharmaceutical Dosage Forms Disperse Systems. Vol. 3. 2nd ed. New York Marcel Dekker, 1998 363. Astarita G. Scale-up overview, closing remarks, and cautions. In Bisio A, Kabel RL, eds. Scale-up of Chemical Processes Conversion from Laboratory Scale Tests to Successful Commercial Size Design. New York Wiley, 1985 678. Gekas V. Transport Phenomena of Foods and Biological Materials. Boca Raton, FL CRC Press, 1992 5-62. 

As Tatterson [55] notes, There is much more volume on scale-up than is typically recognized. This is one feature of scale-up that causes more difficulty than anything else. For disperse systems, a further mechanistic impUcation of the changing volume and surface-area ratios is that particle size reduction (or droplet breakup) is more likely to be the dominant process on a small scale while aggregation (or coalescence) is more likely to be the dominant process on a large scale [55]. 

See Workshop Report Scale-up of liquid and seniisolids disperse systems. G.A. Van Buskirk, V.P. Shah, D. Adair, etal. Pharm. Res. 11 1216-1220, 1994. 

Although the first inclination of the designer might be to scale up the design concept of an existing FAE weapon, that is, to make use of a similar monopropellant fuel (generally liquid), a similar expulsion and dispersion system, and perhaps even a similar type of fuel containment, it becomes evident upon reconsideration that the weapon-configured FAE is not the simplest way to do the job, that the complexities of that type... 

Often interfaces and colloids are discussed together. Colloids are disperse systems, in which one phase has dimensions in the order of 1 nm to 1 pm (see Fig. 1.1). The word colloid comes from the Greek word for glue and has been used the first time in 1861 by Graham1. He applied it to materials which seemed to dissolve but were not able to penetrate a membrane, such as albumin, starch, and dextrin. A dispersion is a two-phase system which is uniform on the macroscopic but not on the microscopic scale. It consists of grains or droplets of one phase in a matrix of the other phase. 

It should be noted that, on one hand, an approach such as this is sufficiently closely related to the fluctuation theory of disperse systems developed in Shishkin s works [73], and on the other hand, it reduces to one of the variants of the flow problems in the percolation theory [78, 79] according to which the probability of the existence of an infinite liquid-like cluster depends on the value of the difference (P — Pcr), where Pcr is the flow threshold. At P < Pcr, only liquid-like clusters of finite dimensions exist which ensure the glassy state of liquid. It is assumed that at P > Pcr and (P — Pcr) 1 the flow probability is of the following scaling form ... 

Matsumoto, T., Hitomi, C., and Onogi, S. 1975. Rheological properties of disperse systems of spherical particles in polystyrene solution at long time-scales. Trans. Soc. Rheol. 194 541. 

Dispersivity is normally determined by laboratory or small-scale field experiments in which a small sample of the aquifer or reservoir is stressed and the results extrapolated to the regional system. This approach has two important limitations (1) dispersivity is scale-dependent (Bredehoeft et al., 1976), i.e. the greater the contrast in hydraulic conductivity the greater will be the values of dispersivity and at present there is no satisfactory way to scale laboratory-derived values to regional sized systems and (2) laboratory samples, by necessity, represent only a minute fraction of the aquifer system. 

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