title: A multi-scale stochastic drug release model for polymer-coated targeted drug delivery systems.
abstract: A multi-scale mathematical model for drug release of oral targeted drug delivery systems was developed and applied to a commercially available delayed release tablet (Asacol) that delivers 5-aminosalicyclic acid (5-ASA) to the colon. Underlying physical and biochemical principles governing the involved processes (diffusion and dissolution) were employed to develop the mathematical description. Finite element formulation was used to numerically solve the model equations. Molecular dynamics (MD) simulations were used to predict macro-scale transport properties of the drug and the biologic fluid. The effect of pH variability in the gastrointestinal tract environment on the dissolution of the polymeric enteric coating was investigated using the Monte Carlo method. The direct coupling method employed (MD) predicted a sufficiently accurate diffusion coefficient (5.7x10(-6) cm2 s-1) of the drug molecules in reasonable (3 h) computation times. The model was validated using experimental data from in vitro dissolution experiments and provided accurate prediction of the drug release from the delivery system (root mean square error of 5%). The amount of drug entering the systemic circulation, computed from the predicted drug release in varying pH environments in the small bowel, was 15-24%. This range was in good agreement with clinical in vivo data (13-36%) obtained from literature. This research shows that in silico experiments using mechanistic models and stochastic approaches can be used for drug design and optimization and as a decision making tool for physicians.
authors.affiliation: Purdue University, Department of Agricultural and Biological Engineering, 225 S. University Street, Room 315, West Lafayette, IN 47907-2093, USA. Electronic address: nhaddis@purdue.edu.
authors.forename: Nahor
authors.initials: N
authors.lastname: Haddish-Berhane
authors.affiliation: Purdue University, Department of Agricultural and Biological Engineering, 225 S. University Street, Room 315, West Lafayette, IN 47907-2093, USA.
authors.forename: Chell
authors.initials: C
authors.lastname: Nyquist
authors.affiliation: Purdue University, Department of Agricultural and Biological Engineering, 225 S. University Street, Room 315, West Lafayette, IN 47907-2093, USA.
authors.forename: Kamyar
authors.initials: K
authors.lastname: Haghighi
authors.affiliation: Purdue University, Department of Agricultural and Biological Engineering, 225 S. University Street, Room 315, West Lafayette, IN 47907-2093, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Corvalan
authors.affiliation: Rush University, St. Luke's Medical Center, Chicago, IL 60612, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.affiliation: Purdue University, Department of Agricultural and Biological Engineering, 225 S. University Street, Room 315, West Lafayette, IN 47907-2093, USA.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Campanella
authors.affiliation: Purdue University, Department of Agricultural and Biological Engineering, 225 S. University Street, Room 315, West Lafayette, IN 47907-2093, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Rickus
authors.affiliation: Rush University, St. Luke's Medical Center, Chicago, IL 60612, USA.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Farhadi
mesh_terms: D000284:Administration, Oral; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003106:Colon; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000706:statistics & numerical data*; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007422:Intestines; D019804:Mesalamine / Q000008:administration & dosage; D015233:Models, Statistical; D009010:Monte Carlo Method; D010316:Particle Size; D011108:Polymers; D013269:Stochastic Processes
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D019804:Mesalamine