It is said that the solubility of a metastable form is difficult or impossible to determine by the usual equilibrium method. In these cases, the solubilities of the metastable form,
Cs'*, (calculated) have been estimated by equation (1).
Cs'*=
Cs(d
C'/d
t)/(d
C/d
t) (1)
where
Cs, d
C/d
t are the solubility and the initial dissolution rate of the stable form., and “
/” is that of the metastable form.
Nogami et al modified the Noyes-Nernst equation to eq. (2), when the dissolution rate is measured by the rotating disk method
d
C/d
t=(
S/
V)
kappCs=(
S/
V){
krkT/(
kr+
kT)}
Cs (2)
where
S is the surface area of disk,
V is the volume of solvent,
kapp is the apparent dissolution rate constant and
kr is the rate constant of the interfacial chemical reaction.
The relationship between
Cs'* and
Cs' is represented by equation (3)
Cs'*=
Cs'
kapp'/
kapp (3)
when
kT is negligible for
kr and
kr',
Cs'* is equal to
Cs'.
When
kT is not negligible for
kr and
kr', the
Cs'* is not equal to
Cs'. The cases in which indomethacin, barbital and phenybutazone,
Cs'* is not equal to
Cs' is discussed.
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