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concentration profi le observed
in vivo
, in order to establish an IVIVC.
In the deconvolution approach, the GastroPlus™ generated
in vivo
dissolution profi le is plotted against the
in vitro
obtained dissolution
profi les, so that 'bioperformance' dissolution condition(s) can be identifi ed.
In the previously described case study of GLK IR tablets (Grbic et al.,
2011), a set of virtual
in vitro
data, based on the experimentally obtained
results (in media pH 1.2, 4.0, 4.5, 6.8, 7.2, and 7.4) and literature
reported data (Hong et al., 1998), was used as the input function in
GastroPlus™ software to estimate the expected GLK plasma concentration
profi les. The investigated
in vitro
profi les (presented in Figure 6.12a)
were generated to refl ect the situation where:
I. less than 85% of the drug is dissolved - incomplete dissolution
(profi le a);
II. more than 85% of the drug is dissolved in 60 min (profi le b);
III. more than 85% of the drug dissolved in 45 min (profi le c);
IV. more than 85% of the drug dissolved in 30 min - 'rapid' dissolution
criteria (profi le d); or
V. more than 85% of the drug dissolved in 15 min - 'very rapid'
dissolution criteria (profi le e).
The corresponding C
p
-time profi les (Figure 6.12b), estimated on the
basis of the generated GLK-specifi c absorption model, were plotted
against the
in vivo
observed data (Najib et al., 2002), in order to develop
a level A IVIVC model (Figure 6.13a). The obtained correlation
coeffi cients and slopes of the regression lines are given in Table 6.10.
The results indicated that variations in drug input kinetics were well
refl ected in the simulated
in vivo
profi les. However, it was evident that
Table 6.10
IVIVC statistical parameters for GLK IR tablets
in vitro
inputs
Convolution approach
Deconvolution approach
a
r
a
r
profi le a
0.440
0.382
2.289
0.875
profi le b
0.894
0.897
1.031
0.894
profi le c
0.896
0.910
1.056
0.929
profi le d
0.898
0.923
0.946
0.896
profi le e
0.867
0.947
1.189
0.999
a - slope of the regression line, r - coeffi cient of correlation
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