Table III.
Physiologically Based Absorption Models Used in GastroPlus Simulations
| Parameter | Value |
|---|---|
| Dosage form | IR: solution or tablet |
| LogP | 1.85 |
| Permeability (×10-4 cm/s) | 1.5 (in silico calculation, verified by in vivo rat data) |
| Solubility (mg/mL) | pH-solubility profile fitted to measured data by GastroPlus (see Fig. 2 for more details) |
| In vivo dissolution | Johnson model for redissolution of precipitate in solution; z-factor dissolution model for tablets |
| Diffusion coefficient (×10−5 cm2/s) | 0.69 (calculated by GastroPlus based on MW) |
| Density (g/mL) | 1.2 (GastroPlus default) |
| Precipitation time (s) | 40,000 (estimated from ASD data) |
| Particle radius (μm) | 25 (for HSWG, RCD tablets), 40 (for RCS tablet) |
| Physiology model | Physiologically fasted human |
| ASF modela | Opt LogD SA/V 6.1 |
aAbsorption scale factor (ASF) is a multiplier used by GastroPlus to scale the effective surface/volume ratio and other absorption rate-determining effects of each compartment. The absorption rate coefficient in each compartment is the product of the Peff and ASF for that compartment. Opt logD Model SA/V 6.1, the current default choice in the program, incorporates pH-partition theory of drug ionization and permeation, and considers the increase in the surface area due to the presence of villi and microvilli in the small intestine