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Four Tests That Decide a Batch: Hardness, Friability, Disintegration, Dissolution

A finished tablet must be strong enough to survive shipping yet fall apart and release its drug on time. Four quality-control tests guard that balance — and dissolution, modelled by Noyes-Whitney, is the one that links a tablet to the patient.

Strong enough, but not too strong

A tablet lives a violent life — tumbling in bottles, riding trucks, dropping through packaging lines. Two tests check that it survives. The hardness test crushes a tablet edge-on and reports the force needed to break it. The friability test tumbles a sample in a rotating drum and weighs the dust lost; under about 1% weight loss usually passes.

Falling apart, then dissolving

The disintegration test drops tablets into baskets that bob up and down in warm fluid and times how long until nothing solid remains on the screen. It is fast and cheap — but it only proves the tablet broke up, not that the drug dissolved. For that you need the deeper test.

The dissolution test is the closest a lab gets to the patient. A tablet sits in a dissolution apparatus — a paddle or basket stirring a vessel of warm medium at body temperature — and you sample the liquid over time to plot how much drug has gone into solution. The medium is kept at far below saturation, a sink condition, so dissolution is never slowed by the drug already released.

Why does stirring, surface area and saturation all matter? Because they are exactly the levers in the Noyes-Whitney equation, the simple law behind dissolution rate. The bigger the exposed surface, the larger the gap from saturation, and the thinner the unstirred layer at the surface, the faster the drug dissolves.

The law behind the curve

Noyes–Whitney:  dC/dt = (D · A / (h · V)) · (Cs − C)

  D  = diffusion coefficient = 6.0e-6 cm^2/s
  A  = surface area exposed   = 2.0 cm^2
  h  = diffusion-layer depth  = 5.0e-3 cm  (50 micrometres)
  V  = dissolution volume     = 900 cm^3   (USP vessel)
  Cs = saturation solubility  = 2.00 mg/cm^3
  C  = drug already dissolved = 0.10 mg/cm^3  (well below Cs => sink)

Initial dissolution rate:
  dC/dt = (6.0e-6 * 2.0) / (5.0e-3 * 900) * (2.00 - 0.10)
        = (1.2e-5) / (4.5)            * (1.90)
        = 2.667e-6 mg/cm^3 per s   (concentration rise in the vessel)

Mass rate = V * dC/dt = 900 * 2.667e-6 = 2.4e-3 mg/s  ~ 0.144 mg/min.

Lesson: halve the particle size and A roughly quadruples, so the
rate quadruples too — which is exactly why micronizing a poorly
soluble drug speeds its dissolution.
A worked Noyes-Whitney dissolution-rate estimate under sink conditions, showing why surface area dominates.