title: Modeling film-coat non-uniformity in polymer coated pellets: a stochastic approach.
abstract: The objective of the present study is to include coating thickness non-uniformity in the development of a drug release model using coated ion-exchange pellets through the use of stochastic approaches. Drug release from ion-exchange resins was described using a Nernst-Plank model. Complexes of a model drug (dextromethorphan) and Dowex 50WX4-200 were prepared using a modified batch method and coated with Kollicoat SR 30D polymer. The deterministic model, validated using experimental drug release profiles for different coating thicknesses at 0%, 10%, 15%, 20% (w/w), was in agreement with the experimental data with a maximum root mean square error (RMSE) of 2.4%. An arbitrary Lagrangian-Eulerian approach was pursued to develop models of spherical pellets with non-uniform coating thicknesses. The Monte Carlo method was used to simulate the effect of the level of coating deformity on the cumulative drug release profile. Considering the co-existence of equal percentages of deformed and undeformed pellets in a batch, the cumulative release profile can vary by approximately +/-6% as a result of coating non-uniformity. The release profile obtained for a model of an arbitrary pellet with an actual non-uniform coating profile was in good agreement with the average release profile for the models of the theoretical randomly deformed pellets. The developed mathematical model is a useful tool to evaluate and predict release profiles of polymer coated ion-exchange resin complexes.
authors.affiliation: Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA. nhaddis@purdue.edu
authors.forename: Nahor
authors.initials: N
authors.lastname: Haddish-Berhane
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Jeong
authors.forename: Kamyar
authors.initials: K
authors.lastname: Haghighi
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D007475:Ion Exchange Resins / Q000737:chemistry*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D009010:Monte Carlo Method; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D015203:Reproducibility of Results; D012117:Resins, Synthetic / Q000737:chemistry; D013269:Stochastic Processes; D013499:Surface Properties
chemical_list: D003692:Delayed-Action Preparations; D007475:Ion Exchange Resins; D011108:Polymers; D011145:Polyvinyls; D012117:Resins, Synthetic; C077982:Dowex 50; C013215:polyvinyl acetate; D003915:Dextromethorphan