Biopharmaceutical importance of particle size

The rate of absorption of many slightly soluble dmgs from the gastrointestinal tract and other sites is limited by the rate of dissolution of the drug. The particle size of a dmg is therefore of importance if the substance in question has a low solubility. 

The Noyes-Whitney equation demonstrates that solubility is one of the main factors determining rate of solution. When the rate of solution is less than the rate of absorption, the solution process becomes rate limiting. Generally speaking, it should become so only when the dmg is of low solubility at the pH of the stomach and intestinal contents. The rate of absorption, the speed of onset of effect and 

The vital influence (for mainly aerodynamic reasons) of particle size in the activity of inhaled drug particles is discussed in Chapter 9, section 9.9. 

The range of substances over which there is pharmacopoeial control of particle size is shown in Table 1.7 sometimes the aim is to achieve uniformity in a product rather than any direct benefit. The control exercised over the particle size of cortisone acetate and griseofulvin is due to their very low solubility the experience is that if the solubility of a dmg substance is about 0.3% or less then the dissolution rate in vivo may be the rate-controlling step in absorption. 

The effect of particle size reduction on dissolution rate is one of exposure of increasing amounts of surface of the drug to the solvent. It is only when comminution reduces particle size below 0.1 m that there is an effect on the intrinsic solubility of the substance (see Chapter 5), and thus on its intrinsic dissolution rate. Very small particles have a very high surface/bulk ratio. If the surface layer has a higher energy than the bulk, as is the case with these small particles, they will interact more readily with solvent to produce higher degrees of solubility. 

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