ABSTRACT
INTRODUCTION Within the last decade, computer-based absorption models have developed to the stage where they are now available as commercial software tools and are being used as a standard tool by scientists working in pharmaceutical research and development. Even before this, mathematical models had been helpful in developing our understanding of how physiological variables, physicochemical properties, and dose and formulation affect oral absorption. A simple early model combined the key compound properties of permeability, ionization, and solubility in an empirical equation delivering a number related to the absorption potential of a drug (1). In the next years numerous more complex models were developed, one of which provided the theoretical basis for the Biopharmaceutical Classification System (2), now widely used to aid decision taking in pharmaceutical formulation development and as the basis for regulatory decisions on biowaivers (3,4). An excellent review of many of the more useful early models has been provided by Yu et al. (5). These models related measurable drug properties and physiological parameters in mathematical formulae, and analytical solution of the equations provided insight into how absorption behavior was expected to change with drug properties. Such models did not rely on the computer. However, the models developed in the last decade are more complex, based on more realistic representations of gastrointestinal tract physiology, and able to track the simultaneous processes of drug transit, dissolution, and transport. As they are too complex for analytical solution they must be solved numerically on the computer to provide a dynamic simulation of the oral absorption process. The development and wider use of such models have clearly been encouraged by the exponential increases in desktop CPU power and today even the most complex simulations involving transit and dissolution of particles of varying sizes, with absorption, metabolism, and distribution of drug in the whole body can be run in seconds on a standard desktop PC.
