Application of Finite Element Modeling (FEM) to Oral Targeted Delivery of Therapeutics A paper from the State-of-the-Art in Application of Finite Element Numerical Solutions to Engineering Problems: A Session Honoring Pioneering Contributions of Professor

Finite element mathematical model for drug release of oral targeted drug delivery systems was developed and applied to a commercially available delayed release dosage form (Asacol®) that delivers 5-aminosalicyclic acid (5-ASA) to the colon. To account for the dissolving and deforming dosage form as it transits the gastrointestinal tract, an Arbitrary Lagrangian-Eulerian (ALE) approach was employed. The effect of regional variability of GIT conditions (pH and transit time) on the dissolution of the delayed release coating and, in turn, on drug release was addressed using Monte-Carlo stochastic approach for healthy and diseased (UC) subjects. The model was validated using experimental data from in vitro dissolution experiments and provided accurate prediction of the drug release from the dosage form (Root Mean Square Error of 5%).Stochastic simulation results indicated that the average small intestinal drug release was 44±19% and 48±21% for healthy and UC subjects, respectively. The systemic absorption of the released drug was estimated to be 10-25% in healthy controls and 11-28% in UC subjects. These results are in good agreement with the clinical in vivo data (13-36% and 17-35% for healthy and UC subjects, respectively). This agreement was also true for 5-ASA and its metabolite (N-acetyl-5-ASA) recovery in the colon. The model can be used for design and optimization of broad range of new and existing targeted and controlled release formulations to the distal intestine and colon.