Computer- aided biopharmaceutical characterization: gastrointestinal absorption simulation - Computer-Aided Applications in Pharmaceutical Technology - page 178

extended biopharmaceutical evaluation can be used to guide formulation
strategy or to predict the effect of food on drug absorption. A growing
concern for biopharmaceutical characterization of drugs/pharmaceutical
products increased the interest in development and evaluation of in silico
tools capable of identifying critical factors (i.e. drug physicochemical
properties, dosage form factors) infl uencing drug in vivo performance,
and predicting drug absorption based on the selected data set(s) of input
factors.
Although an in silico pharmacokinetic (PK) model can confi rm different
drug administration routes (Gonda and Gipps, 1990; Grass and Vee,
1993; Mahar Doan and Boje, 2000), the main focus has been on prediction
of pharmacokinetics of orally administered drugs (Yu et al., 1996; Grass,
1997; Grass and Sinko, 2002; Norris et al., 2000; Agoram et al., 2001;
Boobil et al., 2002). Drug absorption from the gastrointestinal (GI) tract
is a complex interplay between a large number of factors (i.e. drug
physicochemical properties, physiological factors, and formulation related
factors), and its correct representation in the in silico models has been a
major challenge. Various qualitative/quantitative approaches have been
proposed, starting from the pH-partition hypothesis (Shore et al., 1957),
and later moving to the more complex models, such as the Compartmental
Absorption and Transit (CAT) model (Yu and Amidon, 1999). Yu et al.
gave a good review of these models, classifying them into quasi-
equilibrium, steady-state, and dynamic models categories (Yu et al., 1996).
In recent years, substantial effort has been allocated to develop and
promote dynamic models that represent GI tract physiology in view of
drug transit, dissolution, and absorption. Among these are the Advanced
Dissolution, Absorption and Metabolism (ADAM) model, the Grass
model, the GI-Transit-Absorption (GITA) model, the CAT model, and
the Advanced CAT (ACAT) model (Huang et al., 2009). Some of them
have been integrated in commercial software packages, such as
GastroPlus™, SimCYP, PK-Sim ® , IDEA™ (no longer available), Cloe ®
PK, Cloe ® HIA, and INTELLIPHARM ® PKCR (Norris et al., 2000;
www.Simulator.plus.com ; www.Symcyp.com ; Willmann et al., 2003;
www.Cyprotex.com ; www.Intellipharm.com PKCR. One of the fi rst
overviews of the available software intended for in silico prediction of
absorption, distribution, metabolism, and excretion (ADME) properties
was given in the report of Boobis et al. (2002). Cross-evaluation of the
presented software packages was interpreted in terms of software purpose
and function, scientifi c basis, nature of the software, required data to run
the simulations, performance, predictive power, user friendliness,
fl exibility, and evolution possibilities.

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