Learning Objective

•  Principles involved in the formulation of suspensions

The formulation of a suspension involves the following:

1. Medicament: This is the drug with non-aqueous solubility.
2. Flocculating agents: The particles in a suspension should be well dispersed in the vehicle. Dispersion can be improved by adding a surfactant, electrolyte or polymer, which acts as the flocculating agent. The nonionic surfactants act by reducing the surface tension or by forming bridges between the particles. The use of an ionic surfactant to wet the solid could produce either a flocculated or a deflocculated suspension depending on the charge already present on the particle. If the particles have a charge opposite to that of the surfactant, then neutralization occurs and the electrical barrier between the particles is reduced, resulting in flocculation.
   • Electrolytes: These act as flocculating agents by decreasing the electric barrier between the particles due to a decrease in zeta potential. This results in the formation of a bridge between adjacent particles so as to link them together in a loosely arranged structure. The addition of an inorganic electrolyte to an aqueous suspension will alter the zeta potential of the dispersed particles and if this value is decreased flocculation will occur.Examples are sodium salts of acetates, phosphates and citrates.
   • Surfactants: Ionic surface active agents may also cause flocculation by the neutralization of charge on each particle, thus resulting in a flocculated system. Nonionic surfactants adsorb onto more than one particle, thereby forming a loose flocculated structure.
   • Polymers: The linear-branched chain molecules of polymers form a gel-like network within the system, which become adsorbed onto the surfaces of the dispersed particles, thus holding them in a flocculated state.
   Examples are starch, alginates, cellulose derivatives, tragacanth, carbomers and silicates.
3. Deflocculating agents: When the particles have the same charge as that of the surfactant, they repel each other. The particles remain separate, resulting in deflocculation.
4. Suspending agents: These act mainly by increasing the viscosity of the external phase and thus reducing the rate of sedimentation of the dispersed particles. These substances are added to a suspension to increase the viscosity of the continuous phase, so that the particles remain suspended for a sufficiently long time, making it easier to withdraw a uniform dose. The viscosity of the preparation should be such that it can be easily poured from the container and transferred to the site of application. They are also known as thickening agents.The amount of suspending agent used in any given formulation depends on the volume of vehicle being thickened. A suspending agent is intended to increase the viscosity of the vehicle and therefore slow down sedimentation rates. This can also be achieved by decreasing the particle size of the powder in suspension.The following are the most common suspending agents used in extemporaneous dispensing:
   • Tragacanth BP: Used in internal or external suspensions at a concentration of 0.2%
   • Compound tragacanth powder BP (containing 15% tragacanth, 20% acacia, 20% starch and 45% sucrose): Used in internal suspensions at a concentration of 2.0%
   •  Bentonite BP: Used in external suspensions at concentrations of 2%–3% (e.g., calamine lotion)
5. Examples of agents that can be used as suspending agents or thickening agents are given below:
   • Natural polysaccharides
     • Acacia: This acts as a protective colloid and suspending agent and is used in the preparations containing resinous tinctures that precipitate on addition of water. Acacia mucilage becomes acidic on storage as a result of enzyme activity. It also contains an oxidase enzyme, which may cause deterioration of active agents that are susceptible to oxidation.
     • Tragacanth: This is a better thickening agent than acacia. It is used as compound tragacanth powder or tragacanth mucilage.
     • Alginates: These are viscous in nature immediately after preparation, but the viscosity decreases within 24 hours. Alginate mucilages must not be heated above 60°C.
   • Semisynthetic (cellulose derivatives)
     • Methyl cellulose: Used in a concentration of 0.5%–2% as a suspending agent
     •  SCMC (Sodium Carboxymethyl Cellulose): Used in a concentration of 0.25%–1% in products for oral, external and parenteral use
   • Inorganic agents
     • Bentonite: Used in a concentration of up to 3% in preparations for external use such as calamine lotion
     •  Magnesium aluminum silicate (Veegum): Used in a concentration of up to 5%
   • Synthetic compounds
     • Carbomers: Used in a concentration of up to 0.5% for external use
     •  Colloidal silicon dioxide (Aerosil): Used in a concentration of up to 4% for external use
6. Wetting agents: These substances reduce the interfacial tension between the solid particles and the liquid medium, thus producing a suspension of required quality. This is achieved by the addition of a suitable wetting agent that is adsorbed at the solid–liquid interface in such a way that the affinity of the particles towards the surrounding medium is increased, thereby helping in the penetration of liquid into the particles, thus producing good suspension. Examples are spans and tweens.
7. Preservatives: These substances are used to protect the suspension against bacterial growth. The preservatives should be effective against a wide range of microorganisms. They should be chemically and physically compatible with the other ingredients in the formulation. Examples are benzoic acid and methyl and propyl paraben.
8. Organoleptic additives: The following are the various organoleptic additives used in the formulation of a suspension:
   •  Flavoring agents are added to oral preparations. Examples are vanilla, banana, strawberry and pineapple flavors.
   •  Sweetening agents are added to oral preparations. Examples are sucrose, saccharin sodium and aspartame.
   • Coloring agents are added to preparations for oral and external use. Examples are sunset yellow, erythrosine and tartrazine.
   •  Perfumes are used in preparations meant for external use. Examples are rose water and lavender oil.