Pharmaceutical dispersions colloidal systems

Many liquid and semi-liquid pharmaceutical preparations are disperse systems. Disperse systems are defined as systems in which a substance is distributed as particles (discontinuous) into a dispersion medium (continuous). Three types of disperse systems will be discussed which are pharmaceutically relevant colloidal systems, suspensions and emulsions. In both colloidal systems and suspensions, solid particles are dispersed in a liquid. The difference is that in colloidal systems the particles do not settle, while they do in suspensions. This difference is caused by the size of the particles. In colloidal systems, the particles are so small (1 mn - 1 pm) that the Brownian motion (diffusion caused by thermal energy) is stronger than the force of gravity so that they remain suspended in the liquid and do not settle. In suspensions, the particles are larger (>1 pm) and as a consequence the force of gravity is stronger than the Brownian motion which makes them settle (if the density of the particles is larger than that of the dispersion medium). Emulsions consist of non-miscible liquids. Two types of emulsions will be discussed oil drops dispersed in water (oil-in-water emulsion or o/w emulsion) and water drops dispersed in oil (water-in-oil emulsion or w/o emulsion). There are also more complex structures such as w/o/w emulsions and bi-continuous systems. However, these systems will not be discussed. 

Most of the pharmaceutical dispersions can be classified as colloidal systems, although this depends upon... 

Pharmaceutical colloids such as emulsions and suspensions (Fig. 7.1) and aerosols are readily identified (Table 7.1). The disperse phase is the phase that is subdivided. The continuous phase is the phase in which the disperse phase is distributed. Many natural systems such as suspensions of microorganisms, blood, and isolated cells in culture, are also colloidal dispersions. Colloid science is interdisciplinary, for although dealing with complex systems it is nevertheless a unifying discipline as it bridges the physical and... 

It is because of the subdivision of matter in colloidal systems that they have special properties. The large surface-to-volume ratio of the particles dispersed in a liquid medium results in a tendency for particles to associate to reduce their surface area, so reducing their contact with the medium. Emulsions and aerosols are thermodynamically unstable two-phase systems which only reach equilibrium when the globules have coalesced to form one macro-phase, for which the surface area is at a minimum. Many pharmaceutical problems revolve around the stabilisation of colloidal systems. 

Colloidal systems and dispersions are of great importance in oil recovery, waist water treatment, coating, food and beverage industry, pharmaceutical industry, medicine, environmental protection etc. Colloidal systems and dispersions are always multi-component and multiphase systems. In these systems at least one dimension is in a range of colloidal forces action colloidal dispersions/emulsions are examples of three dimensional colloidal systems, while thin liquid films are examples of one dimensional colloidal systems. Mostly colloidal systems are stable because their properties are substantially enhanced by the presence of surfactants and or polymers. The distribution and redistribution of the latter molecules is of the crucial importance for colloidal systems. 

Colloidal systems can be divided into lyophilic and lyophobic systems. Lyophilic colloids have a strong affinity with the dispersion medium by which a solvation shell around the particle is formed. This process is called solvation and if the dispersion medium is water it is called hydration. A polysaccharide dissolved in water is an example of a lyophilic colloidal system. The solvation shell is formed by hydrogen bonds between the hydroxyl groups of the polymer molecules and the water molecules. Pharmaceutical examples are solutions of dextran, used as plasma expanders. Micelles are also lyophilic colloids. Example of such a system is the aqueous cholecalciferol oral mixture (Table 18.15). In these preparations, a lipophilic fluid is dissolved in an aqueous medium by incorporating it in micelles. Because this type of colloids falls apart on dilution to concentrations below the CMC, they are also known as association colloids. Lyophobic colloids have no affinity with the dispersion medium. Thus, in this type of colloids no solvation shell is formed around the particles. An example of lyophobic particles are colloidal gold particles (with a diameter of 1 nm - 1 pm) dispersed in water. There are no... 

Until the beginning of the twenty-first century, in pharmacy, the particles in a colloidal system usually did not consist of active substances but of excipients, such as viscosity enhancers. The number of pubUcations in the pharmaceutical literature on colloidal systems in which the dispersed particles solely consist of a drug substance or consist of carrier systems in which an active substance has been incorporated, however, has increased dramatically in recent years. 

Pharmaceutical suspensions consist of solid particles of variable size dispersed in a liquid medium, generally an aqueous solution. Usually the e of the dispersed particles ranges in the colloidal domain (0,1-10 pm) and this makes pharmaceutical suspensions typical systems where the principles of colloid and -surface science have to be used to deal with their properties. According to Hunter (6). the usual criterion to classify colloidal dispersions concerns mainly the nature of phases forming the system. Table I shows some typical denominations. 

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]. 

JW Vanderhoff, MS El-Aasser. Theory of colloids. In HA Lieberman, MM Rieger, GS Banker, eds. Pharmaceutical Dosage Forms Disperse Systems, Vol. 1,2nd ed. New York Marcel Dekker, 1996, pp 91-152. 

Gilligan, C. A., and Po, A. L. W., Factors affecting Drag Release from a Pellet System Coated with an Aqueous Colloidal Dispersion, Int. J. Pharmaceutics, 73 51-68 (1991)... 

Alany et al. [11,35] reported on the phase behavior of two pharmaceutical ME systems showing interesting viscosity changes. The viscosity of both systems increased with increasing volume fraction of the dispersed phase to 0.15 and flow was Newtonian. However, formation of LC in one of the two systems, namely the cosurfac-tant-free system, resulted in a dramatic increase in viscosity that was dependent on the volume fraction of the internal phase and a change to pseudoplastic flow. In contrast, the viscosity of the bicontinuous ME was independent of water volume fraction. The authors used two different mathematical models to explain the viscosity results and related those to the different colloidal microstructures described. 

Pharmaceutical suspensions are dispersions of solid particles in a suspending medium or vehicle (usually aqueous in nature). When the suspended solids are less than 1 pm, the system is referred to as a colloidal suspension. When the particle sizes are greater than about 1 pm, the system is called a coarse suspension. The practical upper limit for particles in a coarse suspension is approximately 50-75 pm. Depending on the affinity or interaction between the dispersed phase and the dispersion medium, a colloidal dispersion can be classified as lyophilic (hydrophilic) or lyophobic (hydrophobic). ... 

The movement of the pharmaceutical industry away from volatile solvents for coating applications coupled with advancements in coating equipment design led to an increase in the popularity of latex and pseudolatex coating systems. Latexes and pseudolatexes are both colloidal dispersions of polymer droplets in a continuous aqueous phase, the difference between them being that latex systems are formed by emulsion polymerization... 

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. 

The difference between well-known SCF antisolvent techniques such as GAS, PCA, and SEDS usually can be attributed to the specific nozzle mixing (or dispersing) technique involved. Enhanced mass and heat transfer can also be achieved by using mechanical and ultrasonic mixers and ultrafast jet expansion techniques. There are new developments for particle formation by means of dispersed systems such as emulsions, micelles, colloids, and polymer matrixes. It should be emphasized that all these processes involve the same fundamental aspects of mass and heat transfer phenomena between an SCF and a subcritical phase. Clearly the ultimate goal of all SCF particle technologies is to achieve predictable, consistent, and economical production of fine pharmaceuticals or chemicals. This is possible only on the basis of comprehensive mechanistic understanding and well-developed scale-up principles. 

On the other hand, elucidation of the typical components and different forms of the physical. systems that we call pharmaceutical suspensions requires previously to have an idea about the different types of suspensions, intimately related to their purpose and applications. Thus, most authors consider three main kinds of pharmaceutical suspensions (4-6). namely, orally administered, or. simply oral, suspensions externally applied (topical suspensions) and injectable or parenteral. Although strictly speaking, from the colloid science point of view, aerosols ore simply suspensions in which the dispersion medium is a gas and the di.spersed material is. solid, throughout this chapter we will primarily adhere to the more clussicul point of view that considers only solid/liquid dispersions under the denomination of suspensions. Their most significant features are displayed in Table I (see also Refs. 4-6). 

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