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Suspensions: Medicines You Shake Before Use

When a drug refuses to dissolve, suspend it. Learn how to wet stubborn powder, slow settling with Stokes' law, and why a controlled, flocculated suspension redisperses with one shake.

A suspension is two phases

A suspension is a disperse system: solid drug particles (the dispersed phase) scattered through a liquid (the continuous phase) without dissolving. We reach for one when a drug is too insoluble to make a solution, when it tastes too bitter dissolved, or when we want a higher dose than solubility allows in an oral suspension. The price is obvious: solids settle. The art is making sure that when they do, one shake brings them back evenly.

First, the powder must actually get wet. Hydrophobic drug powder floats and clumps, trapping air. A wetting agent — a surfactant that lowers surface tension — lets water displace that air and coat each particle so it sinks and disperses.

Slowing the settling

How fast particles fall is governed by Stokes' law. The settling velocity rises with the square of particle size and with the density difference between solid and liquid, and falls as the viscosity of the medium rises. So you have three honest handles: grind the drug finer, narrow the density gap, or thicken the vehicle.

Stokes' law:  v = d^2 (rho_p - rho_f) g / (18 eta)

Example — drug particle in water:
  d        = 10 um  = 10e-6 m
  rho_p    = 1500 kg/m^3   (drug)
  rho_f    = 1000 kg/m^3   (water)
  g        = 9.81 m/s^2
  eta      = 0.001 Pa.s    (water)

  v = (10e-6)^2 * (1500-1000) * 9.81 / (18 * 0.001)
    = (1e-10) * 500 * 9.81 / 0.018
    = 4.9e-7 / 0.018
    = 2.7e-5 m/s   (~2.7 cm in 1000 s)

Thicken vehicle to eta = 0.020 Pa.s (20x):
  v -> 1.4e-6 m/s   (20x slower)
Halve particle size to 5 um:
  v -> one quarter (d^2): ~6.8e-6 m/s
Stokes' law: settling slows with smaller particles and a thicker, more viscous vehicle.

Flocculated vs deflocculated

Here is the counter-intuitive heart of suspension design. A deflocculated system has fully separated particles repelled by their zeta potential. It looks beautiful at first — slow to settle — but the particles pack down into a dense, hard cake that no amount of shaking will redisperse. A flocculated system deliberately lets particles cling into loose flocs. These settle faster and leave a clearer supernatant, which looks worse on the shelf, but the sediment is fluffy and loose, so one gentle shake brings the whole dose back. For an oral suspension, easy redispersion almost always wins.