Dissolution theory

In order for an active pharmaceutical ingredient to be bioavailable, it has to be dissolved. Thus, solubility and dissolution measurements are  necessary requirements to estimate the drugs bioavailability:
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  • In theory, the intrinsic dissolution rate (IDR) is proportional to the solubility of the compound – i.e. in many cases a very good estimate of IDR can be obtained directly from a solubility measurement: Low solubility = low IDR and vice versa.
  •  It also implies that the dissolution rate is proportional to the solubility (but here the particle size/the surface area of the particles should also be taken into account).
  • However, in some cases the liberation af molecules from the surface into water is not ideal – and the dissolution rate will be lower or higher than theoretically calculated. Thus, in order to determine whether your compound behaves ”ideal”, a measurement of IDR is neccessary.
  • dc/dt = rate of dissolution
  • k = constant
  • Cb =  concentration of the solid in the bulk dissolution medium
  • CS = concentration in the ”diffusion layer” (saturated)
i.e. the higher the concentration at the particle surface the faster the compound will dissolve. At the surface, the solvent will be saturated with the compound molecules which implies that the dissolution rate is directly proportional to the saturated concentration – i.e. the dissolution rate will, in ideal cases, be given by the solubility of the compound. It further implies that you, in theory, are able to calculate the dissolution rate from the particle size/surface area of the particles. However, since these calculations are not straight forward, the dissolution rate is usually measured experimentally. These dissolution measurements are used in product control to secure the same particle behaviour for different batches.