In the development phase, researchers have fewer compounds and more data than in the discovery phase, and the issues are different. Absorption concerns relate more to bioavailability across populations, formulation effects, and for some drugs, controlled release dosage design. GastroPlus™ is designed to help in all three of these areas:
• Evaluate and design dosage formulation
• Evaluate the effects of various controlled release profiles
• Evaluate heterogeneic variations in physiology and transit times
Evaluate and design dosage formulation:
With GastroPlus you can run large numbers of in silico experiments to assess the effects of changing particle size, particle density, and diffusion coefficient on predicted oral absorption.
Evaluate the effects of various controlled release profiles:
GastroPlus allows you to input controlled release profiles as tabulated percent released versus time or as Weibull function parameters that provide time-dependent release. With this capability you can assess the total absorption versus time in the portal vein (and with inputs for first-pass extraction, volume of distribution, and clearance, the blood concentration level versus time) for a wide variety of release profiles. You can also study the sensitivities of percent absorbed to variations in controlled release profile and formulation design.
This capability can guide you in designing a release profile and formulation that achieves desired plasma levels with the least sensitivity to expected variations in physicochemical and physiological parameters.
Evaluate heterogeneous variations in physiology and transit times:
A recent article in Pharmaceutical Research* discusses the need to consider heterogeneity in absorption prediction, especially for drugs with low solubility and low permeability. These drugs transit the entire gastrointestinal tract; therefore, their absorption is more subject to variations in physiology and physicochemical parameters than other drugs. Because drugs must be designed for populations rather than for an ideal average, the ability to assess quickly and cost effectively the effects of expected variations in physiology is important.
GastroPlus can run automatic stochastic simulations (Virtual Trials mode) across distributions of small-intestine transit times and overall effective permeabilities. It also allows the user to manually change inputs affecting both physiology and physicochemical parameters. Through such runs, you can determine the sensitivity of predicted percent absorbed to such variations, and you can assess the effects of changing formulation variables and controlled-release profiles on minimizing the sensitivity of plasma levels to physiological heterogeneity.
Can Your Company Afford to be Without GastroPlus?
We believe the increase in productivity you will realize with GastroPlus will result in significant savings of both time and money. We also believe that the new kinds of information you'll be able to generate with GastroPlus will result in better decisions in allocating scarce resources for both discovery and development.
