Stability suspensions

This is governed by the same forces as those described for other dispersion systems such as emulsions. There are differences, however, as coalescence obviously cannot occur in suspensions and the adsorption of polymers and surfactants also occurs in a different fashion. Flocculation, unlike coalescence, can be a reversible process and partial or controlled flocculation is attempted in formulation. 

Most suspension particles dispersed in water have a charge acquired by specific adsorption of ions or ionization of surface groups, if present. If the charge arises from ionization, the charge on the particle will depend on the pH of the environment. As with other colloidal particles, repulsive forces arise because of the interaction of the electrical double layers on adjacent particles. The magnitude of the charge can be determined by measurement of the electrophoretic mobility of the particles in an applied electrical field. 

The velocity of migration of the particles under unit applied potential is. For 

The rapid clearance of the supernatant in a flocculated system is undesirable in a pharmaceutical suspension. The use of thickeners such as tragacanth, sodium carboxymethylcellulose or bentonite hinders the movement of the particles by 

The attractive forces between suspension particles are considered to be exclusively London-van der Waals interactions (except where interparticle bridging by long polymeric chains occurs). The repulsive forces, as discussed in Chapter 8, comprise both electrostatic repulsion and entropic and enthalpic forces. In aqueous systems the hydrophobic dispersed phase is coated with hydrophilic surfactant or polymer. As adsorption of surfactant or polymer (or, of course, both) at the solid-liquid interface alters the negative charge on the suspension particles, the adsorbed layer may not necessarily confer a repulsive effect. Ionic surfactants may neutralize the charge of the particles and result in their flocculation. The addition of electrolyte such as aluminium chloride can further complicate interpretation of results electrolyte can alter the charge on the suspension particles by specific adsorption, and can affect the solution properties of the surfactants and polymers in the formulation. Some aspects of the application of DLVO theory to pharmaceutical suspensions and the use of computer programmes to calculate interaction curves are discussed by Schneider et al. [4]. 

This concept cannot account for the action shown by many non-ionic, surface-active agents, and in these cases it has been suggested that the size of the agent could lead to repulsion due to steric hindrance, i.e. the molecules extend so far out into the media that two approaching particles do not get close enough to flocculate. 

In non-aqueous media of low dielectric constant ionic charge stabilization is unlikely to be very important. In such cases stabilization depends on steric or entropic repulsion and polymeric agents are preferred 

---

In many colloidal systems, both in practice and in model studies, soluble polymers are used to control the particle interactions and the suspension stability. Here we distinguish tliree scenarios interactions between particles bearing a grafted polymer layer, forces due to the presence of non-adsorbing polymers in solution, and finally the interactions due to adsorbing polymer chains. Although these cases are discussed separately here, in practice more than one mechanism may be in operation for a given sample. 

Suspension Polymerization. Suspension polymerization is carried out in small droplets of monomer suspended in water. The monomer is first finely dispersed in water by vigorous agitation. Suspension stabiUzers act to minimize coalescence of droplets by forming a coating at the monomer—water interface. The hydrophobic—hydrophilic properties of the suspension stabiLizers ate key to resin properties and grain agglomeration (89). 

Ether carboxylates are used not only in powdered detergents but in liquid laundry detergents for their hard water stability, lime soap dispersibility, and electrolyte stability they improve the suspension stability and rheology of the electrolyte builder [130,131]. Formulations based particularly on lauryl ether carboxylate + 4.5 EO combined with fatty acid salt and other anionic surfactants are described [132], sometimes in combination with quaternary compounds as softeners [133,163]. Ether carboxylates show improved cleaning properties as suds-controlling agents in formulations with ethoxylated alkylphenol or fatty alcohol, alkyl phosphate esters or alkoxylate phosphate esters, and water-soluble builders [134]. 

Colloidal suspensions stabilized by electrostatic repulsion are very sensitive to any phenomenon able to disrupt the double layer like ionic strength or thermal motion. 

Stabilization of emulsions Stabilization of suspensions Stabilization of foams Control of crystal growth... 

BA Matthews, CT Rhodes. Use of the Derjaguin, Landau, Verwey and Overbeek theory to interpret pharmaceutical suspension stability. J Pharm Sci 59 521-525, 1970. 

JB Kayes. Pharmaceutical suspensions relation between zeta potential, sedimentation volume and suspension stability. J Pharm Pharmacol 29 199-204, 1977. 

A cosolvent, typically ethanol, may be used to bring drug into solution. A small number of surfactants (sorbitan trioleate, oleic acid, and lecithin) may be dispersed in propellant systems and can aid in suspension stability and in valve lubrication. 

Kaolinite is the main constituent in china clay used to make porcelain. The layers are largely held together by van der Waals forces. Bentonite is used in cosmetics, as a filler for soaps, and as a plasticizer, and it is used in drilling-muds as a suspension stabilizer. Bentonite and kaolinite clays are used, after treatment with sulfuric acid to create acidic surface sites, as petroleum cracking catalysts. Asbestos also has a layered structure (Section 12.13). 

The most widely used theory of suspension stability, the DLVO theory, was developed in the 1940s by Derjaguin and landau (1941) in Russia and by Verwey and Overbeek (1948) in Holland. According to this theory, the stability of a suspension of fine particles depends upon the total energy of interaction, Vt, between the particles. Vf has two components, the repulsive, electrostatic potential energy, Vr, and the attractive force, Va, i. e. 

Dispersants function through various mechanisms. For water-based systems the preferred mechanism is stabilisation by ionic repulsion. A repulsion force layer is formed around the mineral particle. To maintain the suspension stability, the thickness of this layer around each particle has to be increased with increasing particle size. Layer decay is more frequent with the use of small particles, which results in higher proneness to partial flocculation. Also a uniform layer is necessary for effective stabilisation of all dispersed particles. AMP-95 helps to achieve all these requirements. 

The choice of carrier liquid is primarily based on the suspension stability for colloids or solvent goodness for macromolecule solutions. Moreover, surface-charged colloidal particles are also sensitive to ionic strength and addition of surfactants. 

Lastly, particle engineering as a method to improve suspension stability may be an alternative. Weers et al. and Dellamary et al. describe the use of hollow porous particles to decrease the attractive forces between particles in suspension (43,51). The similarities between the particles and the dispersing medium (the propellant system enters and fills the porous particles) reduces the effective Hamaker constant that corresponds to forces of attraction, and also makes the density difference between the propellant and the particles smaller. The FPF of these aerosols was reported to be around 70%. 

In addition to the above, there are emulsion and suspension stabilizers that act as protective colloids and in some cases as thickeners gums (such as acacia and traga canth), alginates, starch and starch derivatives, casein, glue, egg albumin, methyl cellulose, hydrated Mg and Al silicates, etc Refs Same as in previous item... 

Kollidon 30 is also used for this purpose. It can be combined with all conventional suspension stabilizers (thickeners, surfactants, etc.). 

The use of Kollidon CL-M as a suspension stabilizer has nothing whatever to do with the principle of increasing the viscosity. The addition of 5-9% has practically no effect in changing the viscosity, but strongly reduces the rate of sedimentation and facilitates the redis-persability, in particular, an effect that is consistent with the low viscosity. One of the reasons for this Kollidon CL-M effect is its low (bulk) density, which is only half of that of conventional crospovidone, e.g. Kollidon CL. It can clearly be seen from Fig. 5 that a relative volume of sediment of normal micronized crospovidone of high bulk density (= Crospovidone M) is less and more compact that of Kollidon CL-M, which undergoes hardly any sedimentation. 

The polyoxamers, Lutrol F 68 and Lutrol F 127, in concentrations of 2 - 5 %, expressed in terms of the final weight of the suspension, offer a further opportunity of stabilizing suspensions. They also do not increase the viscosity when used in these amounts and can be combined with all other conventional suspension stabilizers. 

Fig. 15.3. LCM suspension stability over time. (Taken from ref. 717. See text for further discussion.)... 

The role of turbulence in assisting with suspension stability is described in Section 10.3.1. For example, a rule of thumb for the role of turbulence in maintaining sufficient suspension stability for mineral flotation is the one-second criterion which states that the particles in a suspension are sufficiently well dispersed for flo-... 

Modern motor oil provides an example of some of the ways in which a number of colloidal and interfacial considerations come into play adhesion and lubrication, detergency, dispersion and suspension stabilization, foam inhibition, and viscosity and its temperature dependence. In addition to providing lubrication, a motor oil is expected to prevent corrosion and aid engine cooling and cleaning. Table 8.1 shows how a number of additives are blended in to help the oil achieve these functions [491]. 

---