Dissolution

The dissolution process is described by the ratio of the GI residence time to the time for complete dissolution. The calculated variable is termed the dissolution number Dn and is given by:

/Vr2-l\

Q.

i Q J/

(3-D

•CJ

where r0 is the initial particle radius (|im)

D is the diffusivity (diffusion coefficient) of the compound (cm2/sec)

p is the density of the compound solid (g/cm3) Cs, Q, R, L are as previously defined

As the residence time exceeds time for complete dissolution (Dn > 1), all material is in solution and is available for absorption. If Dn > 10, then all drug particles are dissolved in a tenth of the transit time and we can comfortably assume that particle size has a limited influence on the fraction absorbed.

For MiMBA, the approximation is made that all particles are of the same size, i.e., mono-dispersed. While in reality this is not the case since a powder contains a distribution of particle sizes, an upper boundary can be established for the initial radius r0 from a microscopic image. The eye is naturally drawn to the larger particles, and these can be used to estimate a 'worst case' r0.

The diffusivity 'D' is a function of molecular size. For a typical small molecule (MW of 300 to 500), D will be about 7 to 8 x10-6 cm2/sec. The density 'p' of an organic solid is typically between 1 to 1.5 g/cm3.

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