For most aqueous solutions, D is typically equal to 5 x 10-6 cm2/sec, p is approximately equal to 1.0 g/mL, so the calculation of equation (51) can be performed if the equilibrium solubility of particles having a known initial particle size is known. Consider a substance whose equilibrium solubility is 1.0 mg/mL. For a particle whose initial diameter equals 10 |J.m, the time to achieve complete dissolution would be predicted to be 25 seconds (0.42 minutes). For the same substance, if the initial diameter instead equaled 50 |J.m, then the time to achieve complete dissolution would be predicted to be 625 seconds (10.4 minutes). For 100 ^m particles of this substance, the time to achieve complete dissolution is calculated to be 2500 seconds (41.7 minutes). The relationship between particle size and the time required to completely dissolve particles of various sizes as defined in equation (51) has been illustrated in Figure 3.
This effect of particle size on dissolution rate of sparingly soluble drug substances has been demonstrated in many instances by the superior dissolution rates observed after size reduction. Examples of compounds studied in such work include methylprednisolone (Higuchi et al., 1963), 1-isopropyl-7-methyl-4-phenylquinazolin-2(1H)-one (Kornblum and Hirschorn, 1970), griseofulvin (Ullah and Cadawader, 1971), monophenylbutazone (Habib and Attia, 1985), nitrofurantoin (Eyjolfsson, 1999), and piroxicam (Swanepoel et al., 2000).
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