0356 ch 021(293-318).ps 3/7/05 8:14 AM Page 293 CHAPTER 21 Colloidal Dispersions Bill J Bowman, PhD Clyde M Ofner III, PhD Hans Schott, PhD The British chemist Thomas Graham applied the term “colloid” An appreciable fraction of atoms, ions, or molecules of col- (derived from the Greek word for glue) ca 1850 to polypeptides loidal particles are located in the boundary layer between the such as albumin and gelatin; polysaccharides such as acacia, particle and the dispersion medium. The boundary layer be- starch, and dextrin; and inorganic compounds such as gelati- tween a particle and air is commonly referred to as a surface; nous metal hydroxides and Prussian blue (ferric ferrocyanide). whereas, the boundary layer between a particle and a liquid or Contemporary colloid and surface chemistry deals with an un- solid is commonly referred to as an interface. The ions/molecules usually wide variety of industrial and biological systems. A few within the particle and within the medium are surrounded on all examples include catalysts, lubricants, adhesives, latexes for side by similar ions/molecules and have balanced force fields; paints, rubbers and plastics, soaps and detergents, clays, ink, however, the ions/molecules at surfaces or interfaces are sub- packaging films, cigarette smoke, liquid crystals, drug delivery jected to unbalanced forces of attraction. Consequently, a surface systems, cell membranes, blood, mucous secretions, and aque- free energy component is added to the total free energy of col- ous humors.1–3 loidal particles and becomes important as the particles become smaller and a greater fraction of their atoms, ions, or molecules are located in the surface or interfacial region. As a result, the solubility of very fine solid particles and the vapor pressure of DEFINITIONS AND CLASSIFICATIONS very small liquid droplets are greater than the corresponding values for coarse particles and drops of the same materials. Colloidal Systems and Interfaces SPECIFIC SURFACE AREA—Decreasing particle size in- Except for high molecular weight polymers, most soluble sub- creases the surface-to-volume ratio, expressed as the specific surface area (Asp ). Specific surface area may expressed as the stances can be prepared as either low molecular weight solu- 2 3 tions, colloidal dispersions, or coarse suspensions depending area (A, cm ) per unit volume (V, cm ) or per unit mass (M, ϭ ␲ 2 ϭ ␲ 3 upon the choice of dispersion medium and dispersion tech- gram). For a sphere, A 4 r and V 4/3 r , then Asp is: 4 nique. Colloidal dispersions consist of at least two phases—one 2 2 A 4␲r 3 cm 3 Ϫ or more dispersed or internal phases, and a continuous or ex- A ϭ ᎏᎏ ϭ ᎏᎏ ϭ ᎏᎏ ᎏᎏ ϭ ᎏᎏ cm 1 sp ␲ 3 3 ternal phase called the dispersion medium or vehicle. Colloidal V 4/3 r r cm r dispersions are distinguished from solutions and coarse disper- For density (d) of the material expressed as g/cm3, the specific sions by the particle size of the dispersed phase, not its compo- surface area is: sition. Colloidal dispersions contain one or more substances that have at least one dimension in the range of 1–10 nm at the A A 4␲r2 3 cm2 lower end, and a few ␮m at the upper end (covering about three Asp ϭ ᎏᎏ ϭ ᎏᎏ ϭ ᎏᎏ ϭ ᎏᎏ ᎏᎏ M Vd 4/3␲r3d rd g orders of magnitude). Thus blood, cell membranes, thinner nerve fibers, milk, rubber latex, fog, and beer foam are colloidal Table 21-1 illustrates the effect of comminution on the specific systems. Some materials, such as emulsions and suspensions of surface area of a material initially consisting of one sphere hav- most organic drugs, are coarser than true colloidal systems but ing a 1-cm radius. The specific surface area increases as the ma- exhibit similar behavior. Even though serum albumin, acacia, terial is broken into a larger number of smaller and smaller and povidone form true or molecular solutions in water, the size spheres. Activated charcoal and kaolin are solid adsorbents of the individual solute molecules places such solutions in the having specific surface areas of about 6 ϫ 106 cm2/g and 104 Ͼ 1–3,5–10 colloidal range (particle size 1 nm). cm2/g, respectively. One gram of activated charcoal has a sur- Several features distinguish colloidal dispersions from face area equal to 1/6 acre because of its extensive porosity and coarse suspensions and emulsions. Colloidal particles are usu- internal voids. ally too small for visibility in a light microscope because at least one of their dimensions measures 1 ␮m or less. They are, how- ever, often visible in an ultramicroscope and almost always in Physical States of Dispersed an electron microscope. Conversely, coarse suspended particles and Continuous Phases are usually visible to the naked eye and always in a light mi- croscope. In addition, colloidal particles, as opposed to coarse A useful classification of colloidal systems is based upon the particles, pass through ordinary filter paper but are retained by state of matter of the dispersed phase and the dispersion dialysis or ultrafiltration membranes. Also, unlike coarse par- medium (ie, whether they are solid, liquid, or gaseous).2,7,8 ticles, colloidal particles diffuse very slowly and undergo little Common examples and various combinations are shown in or no sedimentation or creaming. Brownian motion maintains Table 21-2. The terms sols and gels are often applied to colloidal the dispersion of the colloidal internal phases. dispersions of a solid in a liquid or gaseous medium. Sols tend 293 0356 ch 021(293-318).ps 3/7/05 8:14 AM Page 294 294 PART 2: PHARMACEUTICS Table 21-1. Effect of Comminution on the Specific highly hydrated ions (eg, carboxylate, sulfonate, and alkylam- Surface Area of a Volume of 4␲/3 cm3, Divided into monium ions) and/or organic functional groups that bind wa- Uniform Spheres of Radius Ra ter through hydrogen bonding (eg, hydroxyl, carbonyl, amino, and imino groups). NUMBER OF SPHERES R A (cm2/cm3) sp Hydrophilic colloidal dispersions can be further subdivided 1 1 cm 3 as: 103 0.1 cm ϭ 1 mm 3 10 106 0.1 mm 3 102 True solutions: water-soluble polymers (eg, acacia and povidone). 109 0.01 mm 3 103 Gelled solutions, gels, or jellies: polymers present at sufficiently high 1012 1 ␮m3 104 concentrations and/or at temperatures where their water solubility 1015 0.1 ␮m3 105 is low. Examples include relatively concentrated solutions of gelatin 1018 0.01 ␮m3 106 and starch (which set to gels upon cooling) and methylcellulose (which gels upon heating). 1021 1 nm 3 107 23 8 Particulate dispersions: solids that do not form molecular solutions but 10 0.1 nm 3 10 remain as discrete though minute particles. Bentonite and micro- a Shaded region corresponds to colloidal particle-size range. crystalline cellulose are examples of these hydrosols. Lipophilic or oleophilic substances have a strong affinity for oils. Oils are nonpolar liquids consisting mainly of hydro- carbons having few polar groups and low dielectric constants. to have a lower viscosity and are fluid. If the solid particles form Examples include mineral oil, benzene, carbon tetrachloride, bridged structures possessing some mechanical strength, the vegetable oils (eg, cottonseed or peanut oil), and essential oils system is then called a gel. Prefixes typically designate the dis- (eg, lemon or peppermint oil). Oleophilic colloidal dispersions persion medium. For example, hydrosol (or hydrogel), alcosol include polymers such as polystyrene and unvulcanized or (or alcogel), and aerosol (or aerogel), designate water, alcohol, gum rubber dissolved in benzene, magnesium, or aluminum and air, respectively. stearate dissolved or dispersed in cottonseed oil, and activated charcoal which forms sols or particulate dispersions in all oils. Interaction Between Dispersed Phases LYOPHOBIC DISPERSIONS and Dispersion Mediums The dispersion is said to be lyophobic (solvent-hating) when Ostwald originated another useful classification of colloidal there is little attraction between the dispersed phase and the dispersions based on the affinity or interaction between the dispersion medium. Hydrophobic dispersions consist of parti- dispersed phase and the dispersion medium.2,3,8 This classi- cles that are only hydrated slightly or not at all because water fication refers mostly to solid-in-liquid dispersions. Colloidal molecules prefer to interact with one another instead of solvat- dispersions are divided into the two broad categories, lyophilic ing the particles. Therefore, such particles do not disperse or dis- and lyophobic. Some soluble, low molecular weight substances solve spontaneously in water. Examples of materials that form have molecules with both tendencies and associate in solution, hydrophobic dispersions include organic compounds consisting forming a third category called association colloids. largely of hydrocarbon portions with few, if any, hydrophilic functional groups (eg, cholesterol and other steroids); some non- ionized inorganic substances (eg, sulfur); and oleophilic materi- LYOPHILIC DISPERSIONS als such as polystyrene or gum rubber, organic lipophilic drugs, paraffin wax, magnesium stearate, and cottonseed or soybean The system is said to be lyophilic (solvent-loving) if there is oils. Materials such as sulfur, silver chloride, and gold form hy- considerable attraction between the dispersed phase and the drophobic dispersions without being lipophilic. There is no liquid vehicle (ie, extensive solvation). The system is said to be sharp dividing line between hydrophilic and hydrophobic dis- hydrophilic if the dispersion medium is water. Due to the persions. For example, gelatinous hydroxides of polyvalent met- presence of high concentrations of hydrophilic groups, solids als (eg, aluminum and magnesium hydroxide) and clays such as bentonite, starch, gelatin, acacia, and povidone swell, (eg, bentonite and kaolin) possess some characteristics of disperse, or dissolve spontaneously in water to the greatest both.2,3,6,8 Common lipophobic dispersions include water-in- degree possible without breaking covalent bonds.