A Novel Computational Oral Absorption Simulation Tool to Integrate API Crystal Properties and Drug Product Design Attributes to in Vitro and in Vivo Performance

Purpose:  Develop a Systems-based Pharmaceutics holistic modeling approach to integrate API crystal properties and drug product design attributes to in vitro and in vivo performance . 

Methods:  The gPROMS modeling platform is now used to implement gCOAS (Computational Oral Absorption Simulation ) a novel computational oral absorption modeling tool, with inherent capability for integration with other products available in the same platform.     

Results: gCOAS model has several advanced features for simulating oral absorption.  Features include mass and charge balances of drug species (ionic, non-ionic and micellar) and physiological ions in solution in the gastrointestinal (GI) tract.  A population balance approach is used to represent the particle size distribution of each solid phase either present in the drug product or formed during transit through the GI tract.  Advanced features of nucleation and crystal growth kinetics include calculating the supersaturation with respect to the relevant species forming the solid phase. Drug dissolution is modeled incorporating surface pH of solids, changes in pH of GI tract, and speciation of drug in solution, including solubilization into bile micelles.  The GI tract is modeled based on anatomical segments of which the user can choose to implement any number of sub-segments . Each sub-segment is defined by a residual volume, pH, bile concentration etc.  Additionally all incoming fluids including secretions based on human physiology of GI tract is modeled via rapid re-absorption from the GI wall to attain steady state net water volume.