Stability disperse systems

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]. 

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]. 

Fig. 4. Laser diffraction results of disagglomeration processes after adding compact particles to a stabilized dispersed system (a) and after adding fumed silica suspension (b).

The literature on theories that have been proposed to explain the mechanism by which surfactants stabilize dispersed systems such as foams and emulsions is vast. Here, we will briefly mention one approach that can be related to the loaf volume behavior depicted in Figure 7.10 (MacRitchie 1976,1990). 

Syntactic Cellular Polymers. Syntactic cellular polymer is produced by dispersing rigid, foamed, microscopic particles in a fluid polymer and then stabilizing the system. The particles are generally spheres or microhalloons of phenoHc resin, urea—formaldehyde resin, glass, or siUca, ranging 30—120 lm dia. Commercial microhalloons have densities of approximately 144 kg/m (9 lbs/fT). The fluid polymers used are the usual coating resins, eg, epoxy resin, polyesters, and urea—formaldehyde resin. 

Phenomena at Liquid Interfaces. The area of contact between two phases is called the interface three phases can have only aline of contact, and only a point of mutual contact is possible between four or more phases. Combinations of phases encountered in surfactant systems are L—G, L—L—G, L—S—G, L—S—S—G, L—L, L—L—L, L—S—S, L—L—S—S—G, L—S, L—L—S, and L—L—S—G, where G = gas, L = liquid, and S = solid. An example of an L—L—S—G system is an aqueous surfactant solution containing an emulsified oil, suspended soHd, and entrained air (see Emulsions Foams). This embodies several conditions common to practical surfactant systems. First, because the surface area of a phase iacreases as particle size decreases, the emulsion, suspension, and entrained gas each have large areas of contact with the surfactant solution. Next, because iaterfaces can only exist between two phases, analysis of phenomena ia the L—L—S—G system breaks down iato a series of analyses, ie, surfactant solution to the emulsion, soHd, and gas. It is also apparent that the surfactant must be stabilizing the system by preventing contact between the emulsified oil and dispersed soHd. FiaaHy, the dispersed phases are ia equiUbrium with each other through their common equiUbrium with the surfactant solution. 

P. C. Hiemen2, Principles of Colloid and Suf ace Chemisty, 2nd ed., Marcel Dekker, Inc., New York, 1986 R. D. Void and M. J. Void, Colloid and Inteface Chemisty, Addison-Wesley, Reading, Mass., 1983 H. Sonntag and K. Strenge, Coagulation and Stability of Disperse Systems, Halsted, New York, 1972 D. J. Shaw, Introduction to Colloid and Suf ace Chemisty, 3rd ed., Butterworth, London, 1980. 

By dynamic light scattering it was found that, in surfactant stabilized dispersions of nonaqueous polar solvents (glycerol, ethylene glycol, formamide) in iso-octane, the interactions between reversed micelles are more attractive than the ones observed in w/o microemulsions, Evidence of intermicellar clusters was obtained in all of these systems [262], Attractive intermicellar interactions become larger by increasing the urea concentration in water/AOT/ -hexane microemulsions at/ = 10 [263],... 

A study was made of the comparative stabilities at various exposures of an upset stomach remedy suspension. This product consisted of a dispersion of bismuth subsalicylate and phenylsalicylate in an aqueous system. Methyl-cellulose and magnesium aluminum silicate were selected as the suspending agents, because the presence of polyvalent metallic ions precluded the use of hydrocolloids affected by these ions. In addition, it was found that methyl-cellulose contributed a demulcent effect. The viscosity, as well as the suspension characteristics of the combination of protective colloids used, was of a synergistic nature. These colloids formed a thixotropic system. The thixotropy undoubtedly aids in stabilizing this system. In order to make this product palatable and impart elegance, color and flavor were added. Sample 1 (with protective colloids) showed no separation, while sample 2 (without... 

While drilling low-pressure reservoirs with nonconventional methods, it is conunon to use low-density dispersed systems, such as foam, to achieve underbalanced conditions. To choose an adequate foam formulation, not only the reservoir characteristics but also the foam properties need to be taken into account. Parameters such as stability of foam and interactions between rock-fluid and drilling fluid-formation fluid are among the properties to evaluate while designing the drilling fluid [13]. 

Content uniformity and long-term stability of a pharmaceutical product are required for a consistent and accurate dosing. Aggregation of dispersed particles and resulting instabilities such as flocculation, sedimentation (in suspensions), or creaming and coalescence (in emulsions) often represent major problems in formulating pharmaceutical disperse systems. 

Surfactants are useful in formulating a wide variety of disperse systems. They are required not only during manufacture but also for maintaining an acceptable physical stability of these thermodynamically unstable systems. Besides the stabilizing efficiency, the criteria influencing the selection of surfactants for pharmaceutical or cosmetic products include safety, odor, color, and purity. 

A properly formulated disperse system should exhibit an acceptable physical stability over a wide range of... 

For suspensions primarily stabilized by a polymeric material, it is important to carefully consider the optimal pH value of the product since certain polymer properties, especially the rheological behavior, can strongly depend on the pH of the system. For example, the viscosity of hydrophilic colloids, such as xanthan gums and colloidal microcrystalline cellulose, is known to be somewhat pH- dependent. Most disperse systems are stable over a pH range of 4-10 but may flocculate under extreme pH conditions. Therefore, each dispersion should be examined for pH stability over an adequate storage period. Any... 

The determination of the zeta potential of particles in a disperse system provides useful information concerning the sign and magnitude of the charge and its effect on the stability of the system (see Sec. II.B) [56, 206 208], It can be of value in the development of pharmaceutical suspensions, particularly if the... 

The preparation of satisfactory disperse systems consists of three main steps preparing the internal phase in the proper size range, dispersing the internal phase in the dispersion medium, and, finally, stabilizing the resultant product. These three steps may be done sequentially, but in many cases (e.g., emulsions), they are usually done simultaneously. 

Investigations of the rheological properties of disperse systems are very important both from the fundamental and applied points of view (1-5). For example, the non-Newtonian and viscoelastic behaviour of concentrated dispersions may be related to the interaction forces between the dispersed particles (6-9). On the other hand, such studies are of vital practical importance, as, for example, in the assessment and prediction of the longterm physical stability of suspensions (5). 

This model was introduced by Neville and Hunter (13,14) for the case of sterically stabilized dispersions which have undergone reversible flocculation. It is assumed that the major contribution to the excess energy dissipation in such pseudoplastic systems comes from the need to provide energy from the shear field to separate contacting particles. Under these conditions, the extrapolated yield value is given by the expression (13,32,33),... 

An emulsion is a dispersed system of two immiscible phases. Emulsions are present in several food systems. In general, the disperse phase in an emulsion is normally in globules 0.1-10 microns in diameter. Emulsions are commonly classed as either oil in water (O/W) or water in oil (W/O). In sugar confectionery, O/W emulsions are most usually encountered, or perhaps more accurately, oil in sugar syrup. One of the most important properties of an emulsion is its stability, normally referred to as its emulsion stability. Emulsions normally break by one of three processes creaming (or sedimentation), flocculation or droplet coalescence. Creaming and sedimentation originate in density differences between the two phases. Emulsions often break by a mixture of the processes. The time it takes for an emulsion to break can vary from seconds to years. Emulsions are not normally inherently stable since they are not a thermodynamic state of matter. A stable emulsion normally needs some material to make the emulsion stable. Food law complicates this issue since various substances are listed as emulsifiers and stabilisers. Unfortunately, some natural substances that are extremely effective as emulsifiers in practice are not emulsifiers in law. An examination of those materials that do stabilise emulsions allows them to be classified as follows ... 

Stumm, W., C. P. Huang, and S. R. Jenkins (1970), "Specific Chemical Interaction Affecting the Stability of Dispersed Systems", Croat. Chem. Acta 42, 223-245. 

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

An L-L-S system based on PEG, is, for example, the one described by Leitner and co-workers, where the ability of PEGs to stabilize dispersed Pd-nanoparticles was coupled with the use of SCCO2. The model reaction that was investigated in this system was the oxidation of alcohols with oxygen in the presence of Pd-clusters of structure [Pd56i-phen6o(OAc)igo] (phen = 1,10-phenanthroline) (Figure 6.14)." °... 

---