Solid dispersion system

Most paint formulations consist of disperse systems (solid in liquid dispersions) [2]. The disperse phase consists of primary pigment particles (organic or inorganic) which provide the opacity, colour and other optical effects these are usually in the submicron range. Other coarse particles (mostly inorganic) are used in primers and undercoats to seal the substrate and enhance adhesion of the top coat The continuous phase consists of a solution of polymer or resin which provides the basis for a continuous film that seals the surface and protects it from the outside environment Most modem paints contain latexes which are used as film formers. These latexes - which typically have a glass transition temperature (Tg) below... 

Dissolution of 5 could be enhanced in H2O by solid dispersion systems with urea and mannitol (97MI27). A method for solubilizing 5 and 6 at near physiological pH was patented (98EUP856316). Solubility characteristics of 5 was investigated in an in vitro tear model (98MI24). 

Dispersed Noninhibited Systems. Drilling fluid systems typically used to drill the upper hole sections are described as dispersed noninhibited systems. They would typically be formulated with freshwater and can often derive many of their properties from dispersed drilled solids or bentonite. They would not normally be weighted to above 12 Ib/gal and the temperature limitation would be in the range of 176-194°F. The flow properties are controlled by a deflocculant, or thinner, and the fluid loss is controlled by the addition of bentonite and low viscosity CMC derivatives. 

It should be noted that this is quite an unusual law, since in other known cases durability of solids is expressed by stronger laws, namely, exponential or power laws. Thus, in the given example we cannot give a unified definition of yield stress. The work cited is the only published observation of the durability of a filler s structure in dispersion systems. Therefore at present it is difficult to say how much such phenomena are typical for filled polymers, but we cannot exclude them. 

Gas-filled plastics are polymer materials — disperse systems of the solid-gas type. They are usually divided into foam plastics (which contain mostly closed pores and cells) and porous plastics (which contain mostly open communicating pores). Depending on elasticity, gas-filled plastics are conventionally classified into rigid, semi-rigid, and elastic, categories. In principle, they can be synthesized on the basis of any polymer the most widely used materials are polystyrene, polyvinyl chloride, polyurethanes, polyethylene, polyepoxides, phenol- and carbamideformaldehyde resins, and, of course, certain organosilicon polymers. 

In terms of the two-phase system which comprises dispersions of solids in liquids, the minimum energy requirement is met if the total interfacial energy of the system has been minimized. If this requirement has been met, chemically, the fine state of subdivision is the most stable state, and the dispersion will thus avoid changing physically with time, except for the tendency to settle manifest by all dispersions whose phases have different densities. A suspension can be stable and yet undergo sedimentation, if a true equilibrium exists at the solid-liquid interface. If sedimentation were to be cited as evidence of instability, no dispersion would fit the requirements except by accident—e.g., if densities of the phases were identical, or if the dispersed particles were sufficiently small to be buoyed up by Brownian movement. 

A disperse system is defined as a heterogenous, two-phase system in which the internal (dispersed, discontinuous) phase is distributed or dispersed within the continuous (external) phase or vehicle. Various pharmaceutical systems are included in this definition, the internal and external phases being gases, liquids, or solids. Disperse systems are also important in other fields of application, e.g., processing and manufacturing of household and industrial products such as cosmetics, foods, and paints. 

This chapter describes the basic principles involved in the development of disperse systems. Emphasis is laid on systems that are of particular pharmaceutical interest, namely, suspensions, emulsions, and colloids. Theoretical concepts, preparation techniques, and methods used to characterize and stabilize disperse systems are presented. The term particle is used in its broadest sense, including gases, liquids, solids, molecules, and aggregates. The reader may find it useful to read this chapter in conjuction with Chapters 8, 12, and 14, since they include some of the most important applications of disperse systems as pharmaceutical dosage forms [1]. 

Disperse systems can be classified in various ways. Classification based on the physical state of the two constituent phases is presented in Table 1. The dispersed phase and the dispersion medium can be either solids, liquids, or gases. Pharmaceutically most important are suspensions, emulsions, and aerosols. (Suspensions and emulsions are described in detail in Secs. IV and V pharmaceutical aerosols are treated in Chapter 14.) A suspension is a solid/liquid dispersion, e.g., a solid drug that is dispersed within a liquid that is a poor solvent for the drug. An emulsion is a li-quid/liquid dispersion in which the two phases are either completely immiscible or saturated with each other. In the case of aerosols, either a liquid (e.g., drug solution) or a solid (e.g., fine drug particles) is dispersed within a gaseous phase. There is no disperse system in which both phases are gases. 

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. 

The common concentration of a surfactant used in a formulation varies from 0.05 to 0.5% and depends on the surfactant type and the solids content of the dispersion. In practice, very often combinations of surfactants rather than single agents are used to prepare and stabilize disperse systems. The combination of a more hydrophilic surfactant with a more hydrophobic surfactant leads to the formation of a complex film at the interface. A good example for such a surfactant pair is the Tween-Span system of Atlas-ICI [71]. 

The same group reported in 1986 a sensitive and selective HPLC method employing CL detection utilizing immobilized enzymes for simultaneous determination of acetylcholine and choline [187], Both compounds were separated on a reversed-phase column, passed through an immobilized enzyme column (acetylcholine esterase and choline oxidase), and converted to hydrogen peroxide, which was subsequently detected by the PO-CL reaction. In this period, other advances in this area were carried out such as the combination of solid-state PO CL detection and postcolumn chemical reaction systems in LC [188] or the development of a new low-dispersion system for narrow-bore LC [189],... 

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. 

For many dispersed systems (gas bubbles in liquids, liquid droplets in another liquid, solid particles in a liquid), it has been found that the slip velocity is related to the terminal velocity u, of a single bubble, droplet or particle by the equation... 

Atoms (or molecules) on the surface of a condensed (solid or liquid) phase have the excessive free energy compared to the atoms in the bulk. This is the key factor that determines the ability of highly dispersed systems for the spontaneous decrease of the excessive free energy any time when possible. 

In this group of disperse systems we will focus on particles, which could be solid, liquid or gaseous, dispersed in a liquid medium. The particle size may be a few nanometres up to a few micrometres. Above this size the chemical nature of the particles rapidly becomes unimportant and the hydrodynamic interactions, particle shape and geometry dominate the flow. This is also our starting point for particles within the colloidal domain although we will see that interparticle forces are of great importance. 

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. 

Dispersed Systems. Many fluids of commercial and biological importance are dispersed systems, such as solids suspended in liquids (dispersions) and liquid—liquid suspensions (emulsions). Examples of the former include inks, paints, pigment slurries, and concrete examples of the latter include mayonnaise, butter, margarine, oil-and-vinegar salad dressing, and milk. Blood seems to fall in between as it is a suspension of deformable but not liquid particles, and it does not behave like either a dispersion or an emulsion (69) it thus has an interesting rheology (70). 

Dispersion of a solid or liquid in a liquid affects the viscosity. In many cases Newtonian flow behavior is transformed into non-Newtonian flow behavior. Shear thinning results from the ability of the solid particles or liquid droplets to come together to form network structures when at rest or under low shear. With increasing shear the interlinked structure gradually breaks down, and the resistance to flow decreases. The viscosity of a dispersed system depends on hydrodynamic interactions between particles or droplets and the liquid, particle-particle interactions (bumping), and interparticle attractions that promote the formation of aggregates, floes, and networks. 

This is because the effect of the dispersed solid, rather than the dispersing medium, is usually more significant. However, the latter should not be ignored. Many industrial problems involving unacceptably high viscosities in dispersed systems are solved by substituting solvents of lower viscosity. 

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