Suspensions
Upon completion of this exercise, you should be able to:
- Define and describe the physical characteristics of pharmaceutical suspensions.
- Define flocculation and aggregation.
- Identify a stable (flocculated) suspension, by visual inspection or by verbal description of its appearance and physical characteristics.
- Describe the effect of viscosity on the sedimentation rate of suspensions.
- Identify/describe the role of formulation aids in the preparation of suspensions. (e.g., electrolytes, viscosity enhancers).
- Characterize the desired rheological behavior of suspensions.
- Prepare, label, and dispense a suspension.
The term “suspension” refers to a two-phase system consisting of a finely divided solid dispersed (suspended) in a liquid (the dispersing medium). Gels, magmas, and mucilages also contain suspended particles but are different from suspensions in that these suspended particles create a three-dimensional structure of interlacing particles or solvated macromolecules that restrict the movement of the dispersing medium.
Suspensions are intended for oral administration as sweetened, flavored formulations or for topical application where they are referred to as “lotions.” Fluid liquid emulsions are also generically called lotions. Suspensions are also used as non-sweetened, non-flavored formulations for many parenteral routes of administration (e.g., intraocular, intranasal, IV, IM, ID, SC). Gels can be used to administer medications orally, topically, vaginally, and rectally.
Suspensions possess certain advantages over other dosage forms. Some drugs are insoluble in all acceptable media and must, therefore, be administered as a tablet, capsule, or as a suspension. Because of their liquid character, suspensions represent an ideal dosage form for patients who have difficulty swallowing tablets or capsules. This factor is of particular importance in administration of drugs to children. Suspensions of insoluble drugs may also be used externally, often as protective agents.
In addition, disagreeable tastes can be masked by a suspension of the drug or a derivative of the drug, an example of the latter being the drug chloramphenicol palmitate. Finally, drugs in suspension are chemically more stable than in solution. This is particularly important with certain antibiotics and the pharmacist is often called on to prepare such a suspension just prior to the dispensing of the preparation.
Suspensions also possess some disadvantages relative to other dosage forms. The primary disadvantage is their physical instability; i.e., that they tend to settle over time leading to a lack of uniformity of dose. This can, however, be minimized by careful formulation and by shaking the suspension before each dose is delivered. An additional disadvantage is that the texture of suspensions may be unpleasant to patients and should be carefully considered during formulation.
Formulating Stable Suspensions
Physical stability in suspensions is controlled by (1) the addition of flocculating agents to enhance particle “dispersability” and (2) the addition of viscosity enhancers to reduce sedimentation rate in the flocculated suspension.
Flocculating agents are electrolytes which carry an electrical charge opposite that of the net zeta potential of the suspended particles. The addition of the flocculating agent, at some critical concentration, negates the surface charge on the suspended particles and allows the formation of floccules or clusters as particles are held loosely together by weak van der Waals forces. Since the particles are linked together only loosely, they will not cake and may be easily redispersed by shaking the suspension. Floccules have approximately the same size particles; therefore a clear boundary is seen when the particles settle.
The rate of sedimentation of a suspended phase depends on several factors which may be controlled by pharmaceutical manipulation. Assuming that all dispersed particles are of uniform shape and size and that the particles are sufficiently far apart so that the movement of one does not affect the neighboring particles, the rate of sedimentation can be estimated by Stoke’s equation:
where:
V is the sedimentation rate (cm/sec)
d the diameter of the suspended particles (cm)
r1 the suspended particle density
r2 the density of the medium (g/cm3)
g is the acceleration of gravity (980.7 cm/sec2)
ho is the viscosity of the external phase in poises (g/cm sec).
Although the Stokes’ equation does not consider all the variables which affect the stability of a suspension, it gives an approximation of the settling rate and an appreciation of the variables governing the sedimentation process. For example, by reducing the particle size or by increasing the viscosity and density of the external phase, the rate of sedimentation can be retarded.
As we can see from Stoke’s Law, if we apply flocculation as a means of preventing caking, then we will increase the particle diameter, and thus increase the rate of sedimentation. Now we need some means to reduce this rate of settling, so that the suspension can be accurately dosed before it begins to settle. Practically speaking, the viscosity of the dispersion medium is the only other Stoke’s variable affecting sedimentation rate over which the pharmacist can exert any control. Suspending or thickening agents are added to suspensions to thicken the suspending medium, thereby reducing the movement (sedimentation) of suspended particles and physically stabilizing the product. This is particularly important in flocculated systems in which rapid particle settling is the primary factor leading to physical instability and lack of dosage uniformity in the product.
Ideally, the system should (rheologically) be pseudoplastic; that is, it should have high viscosity at low shear rates (during storage) and low viscosity at high shear rates (during shaking, pouring, or spreading). Suspending agents which are thixotropic as well as pseudoplastic are desirable, since they recover slowly from the deformation that occurs through shearing (i.e. upon shaking, they remain fluid long enough to be poured and spread).
Viscosity Enhancers
Viscosity enhancers include agents from each of the following categories. Typically, the concentrations used range from 0.5% to 5%, but the needed viscosity will depend on the suspended particle’s tendency to settle.
- Natural hydrocolloids
Acacia, tragacanth, alginic acid, carrageenan, locust bean gum, guar gum, gelatin. - Semisynthetic hydrocolloids
Methylcellulose, sodium carboxymethylcellulose - Synthetic hydrocolloids
Carbopol® - Clays
Bentonite, Veegum®
Niacin Suspension: scenario and formulation record
Rifampin Suspension: scenario and formulation record
Zinc Oxide and Talc Lotion: scenario and formulation record