Modeling film-coat non-uniformity in polymer coated pellets: a stochastic approach

Int J Pharm. 2006 Oct 12;323(1-2):64-71. doi: 10.1016/j.ijpharm.2006.05.064. Epub 2006 Jun 6.

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.

MeSH terms

  • Algorithms
  • Computer Simulation
  • Delayed-Action Preparations / chemistry*
  • Dextromethorphan / administration & dosage
  • Dextromethorphan / chemistry
  • Dextromethorphan / pharmacokinetics*
  • Drug Delivery Systems / methods
  • Ion Exchange Resins / chemistry*
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Models, Chemical*
  • Monte Carlo Method
  • Polymers / chemistry*
  • Polyvinyls / chemistry
  • Reproducibility of Results
  • Resins, Synthetic / chemistry
  • Stochastic Processes
  • Surface Properties

Substances

  • Delayed-Action Preparations
  • Ion Exchange Resins
  • Polymers
  • Polyvinyls
  • Resins, Synthetic
  • Dowex 50
  • polyvinyl acetate
  • Dextromethorphan