TY - JOUR
T1 - Modeling film-coat non-uniformity in polymer coated pellets
T2 - A stochastic approach
AU - Haddish-Berhane, Nahor
AU - Jeong, Seong Hoon
AU - Haghighi, Kamyar
AU - Park, Kinam
PY - 2006/10/12
Y1 - 2006/10/12
N2 - 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.
AB - 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.
KW - Coated pellets
KW - Coating non-uniformity
KW - Ion-exchange
KW - Mathematical modeling
KW - Numerical methods
KW - Sustained release
UR - http://www.scopus.com/inward/record.url?scp=33748685962&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2006.05.064
DO - 10.1016/j.ijpharm.2006.05.064
M3 - Article
C2 - 16831526
AN - SCOPUS:33748685962
SN - 0378-5173
VL - 323
SP - 64
EP - 71
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -