Pharmaceutical dispersions colloid stability

Electrostatic and electrical double-layer forces play a very important role in a number of contexts in science and engineering. As we see in Chapter 13, the stability of a wide variety of colloids, ranging from food colloids, pharmaceutical dispersions, and paints, to colloidal contaminants in wastewater, is affected by surface charges on the particles. The filtration efficiency of submicron particles can be diminished considerably by electrical double-layer forces. As we point out in Chapter 13, coagulants are added to neutralize the electrostatic effects, to promote aggregation, and to enhance the ease of separation. 

The sedimentation of pharmaceutical dispersions in non-Newtonian polymer solutions is of some practical interest. These polymers are used not only to stabilize colloidal particles but also to slow down (or prevent) settling, thus preventing cake formation. Newtonian fluids are defined as simple fluids that show a linear relationship between the rate of flow or shear (G) and the applied (or shearing) stress (F) at a constant viscosity (p) as shown in Figure 4.38 ... 

For decades the problem of stability has plagued colloid chemists and others engaged in the manufacture and use of dispersions. Only a determined practical approach to the solution of this problem has been responsible for the modest accumulation of theoretical knowledge in existence today. In the field of dispersions, for example, problems of physical instability have been solved for paints, pharmaceuticals, adhesives, asphalt, detergents, and commodities used in the graphic arts, in addition to the numerous successful encounters with instability (or sometimes with undesired stability) in the food industry. 

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]. 

Micelles are colloidal dispersions that form spontaneously, under certain concentrations, from amphiphilic or surface-active agents (surfactants), molecules of which consist of two distinct regions with opposite afL nities toward a given solvent such as water (Torchilin, 2007). Micelles form when the concentration of these amphiphiles is above the critical micelle concentration (CMC). They consist of an inner core of assembled hydrophobic segments and an outer hydrophilic shell serving as a stabilizing interface between the hydrophobic core and the external aqueous environment. Micelles solubilize molecules of poorly soluble nonpolar pharmaceuticals within the micelle core, while polar molecules could be adsorbed on the micelle surface, and substances with intermediate polarity distributed along surfactant molecules in intermediate positions. 

Emulsions and suspensions are disperse systems that is, a liquid or solid phase is dispersed in an external liquid phase. While emulsions are sometimes formulated from oily drugs or nutrient oils their main function is to provide vehicles for drug delivery in which the drug is dissolved in the oil or water phase. Suspensions, on the other hand, are usually prepared from water-insoluble drugs for delivery orally or by injection, usually intramuscular injection. An increasing number of modern delivery systems are suspensions - of liposomes or of polymer or protein microspheres, nanospheres or dendrimers, hence the need to understand the formulation and stabilization of these systems. Pharmaceutical emulsions and suspensions are in the colloidal state, that is where the particles range from the nanometre size to visible (or coarse) dispersions of several micrometres. 

As mentioned above, the first requirement to produce a pharmaceutical suspension is to achieve adequate wetting of the solid particles by the liquid vehicle. Furthermore, the stability of the suspension demands that the energy of interact tion between the dispersed particles be repulsive or, in thermodynamic terms, that the total free energy of interaction between the particles (AGni) be po.sitive. Wetting of particles di.spersed in water is closely related to their hydrophilicity or hydrophobicity. These concepts are frequently employed in a qualitative way. and not always scientifically correct, as water loving" or not. In this section the terms "hydrophilic colloids and "hydrophobic colloids will be described on a more quantitative basis. 

V. Nakamoto. M. Hashida, S. Muranishi, and H. Sezaki. Studies on pharmaceutical modiheation of anticancer agents. II. Enhanced delivery of bleomycin into lymph by emulsions and drying emulsions. Chem. Pharm. Bull., 23 3125-3131. 1975. D. H. Napper. Polymer Stabilization of Colloidal Dispersion.s. London. Academic Press, 1983. 

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