Computer- aided biopharmaceutical characterization: gastrointestinal absorption simulation - Computer-Aided Applications in Pharmaceutical Technology - page 214

In the case of IR tablets, the employed media included water, 0.1, 0.25,
0.5, and 1% sodium lauryl sulfate (SLS) aqueous solution, 0.1 M HCl,
USP acetate buffer pH 4.5, and USP phosphate buffer pH 6.8. In the case
of CR tablets, drug release studies were performed in water, 1% SLS, and
according to the half-change methodology (HCM). The obtained
dissolution data were later used as the input function in the GastroPlus™
Single Simulation Mode, to evaluate the infl uence of in vitro drug
dissolution rate on the predicted CBZ plasma concentration-time profi les.
The dissolution profi les used as inputs, and the corresponding C p -time
profi les, are presented in Figure 6.14. PK parameters predicted on the
basis of different input CBZ dissolution rates and the relevant prediction
error statistics are given in Tables 6.11 and 6.12. Figures 6.14b and d
illustrate that, in the case of CBZ IR tablets, the simulated in vivo profi les

The PK parameters predicted based on CBZ IR tablets
dissolution in various media

Table 6.11

Dissolution
media

C max
(mg/L)

% PE AUC 0 → t AUC 0 → ∞ % PE t max (h) F a (%)

(μg h/mL) (μg h/mL)

pH 6.8 3.29 -12.96 194.4 220.9 -3.58 16.5 95.5

0.1% SLS 3.60 -4.76 199.7 225.8 -1.44 10.5 97.6

0.25% SLS 3.61 -4.5 200.6 226.5 -1.13 9.9 98.9

0.5% SLS 3.79 0.26 202.1 227.7 -0.61 6.6 98.4

1% SLS 3.77 -0.26 201.9 227.5 -0.70 6.9 98.3

In vivo obs* 3.78 224.6 229.1 6.0 N/A

* Refers to the data obtained/calculated based on the mean C p -t profi le observed for
the reference product in the relevant in vivo BE study.

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￿ ￿

The PK parameters predicted based on CBZ CR tablets
dissolution in various media

Table 6.12

Dissolution
media

C max
(mg/L)

% PE AUC 0 → t AUC 0 → ∞ % PE t max (h) F a (%)

(μg h/mL) (μg h/mL)

Water 2.06 −35.42 131.6 143.2 −39.37 21.2 59.6

Half-change
method

3.45 8.15 210.6 228.1 −3.43 13.8 95.6

1% SLS 3.56 11.60 215.6 232.8 −1.44 9.9 97.5

In vivo obs* 3.19 223.9 236.2 14.0 N/A

* Refers to the data obtained/calculated based on the mean C p -t profi le observed for
the reference product in the relevant in vivo BE study.