Formulation practical - Suspensions.

28th November 2003

Formulation practical – Suspensions

Introduction

A suspension is a coarse dispersion in which insoluble solid particles are dispersed in a liquid medium. Particle diameter is generally greater than 0.1μm. The essential point is that a drug prepared as a suspension will be in a solid form even though the dosage form as a whole is liquid. Suspensions are a widely used type of dosage form, for oral, inhalation, topical, ocular and, in some cases, parental administration.

Drugs are formulated as suspensions because of their poor solubility, ease of swallowing and flexibility of administered dose. They have an increased chemical stability and a less noticeable taste as compared to a solution formulation. The limitation of formulating a drug as a suspension is that it needs to be shaken prior to measuring the dose, to re-suspend the suspension to gain an accurate dose.

Over time, the solid particles tend to settle; the rate of sedimentation (v) is given by Stoke’s Law:

v = 2gr2 (ρd - ρc)

9η

where: g = acceleration due to gravity

r = radius of the particle

ρd = density of the disperse phase

ρc = density of the continuous phase

η = viscosity of the continuous phase

Rate of sedimentation can be decreased by reducing particle size, reducing the density difference or by increasing the viscosity of the dispersed phase. Reducing the size of the suspended particles results in a slower settling rate. One big problem with fine particles, however, is the fact that when they settle, the form a more closely packed sediment, which may be more difficult to re-disperse. The slow rate of settling prevents the entrapment of liquid within the settlement, which thus becomes more compacted. This phenomenon is called caking and is the most serious physical stability problem encountered in suspension formulations.

One way to prevent caking is by the addition of flocculating agents such as electrolytes, surfactants, polymeric flocculating agents, e.g. starch, alginates. Flocculating agents work by causing the solid particles to aggregate and form flocs (clusters) in a loose open structure. Polymers adsorb onto particles and cause inter-particle bridging to cause flocculation. Electrolytes cause flocculation by reducing the charge on particles. Floc formation is enabled. Addition of excess electrolytes, however, can reverse the charge; the repulsive forces cause de-flocculation.

In the flocculated system, the flocs behave as a single unit, the latter is larger, thus settling occurs at a faster rate. However, when the flocs settle, large amounts of the continuous phase are entrapped in the sediment. The volume of the sediment is thus larger, and the suspension is easier to re-suspend, i.e. caking does not occur.

Experiment A – to prepare a range of Calamine suspensions and determine the effects of various additives on the stability of the suspensions

Aim