The effect of experimental design on the modeling of a tablet coating formulation using artificial neural networks.
The aim of this study was to investigate the effect of experimental design strategy on the modeling of a film coating formulation by artificial neural networks (ANNs). Box-Behnken, central composite and pseudo-random designs of 102, 90 and 100 simulated records, respectively were used to train a multilayer perceptron (MLP) ANN comprising six input and two output nodes separated by a single hidden layer of five nodes. Network over-training was limited by using a test set of 40 pseudo-randomly distributed records. The models were validated using a set of 60 pseudo-randomly distributed records. Crack velocity was highly curved with respect to pigment particle size and size distribution. Similarly, film opacity was highly curved in response to pigment concentration and film thickness. The Box-Behnken and central composite designs generated models that were unable to predict crack velocity and showed extensive bias in prediction of film opacity. The pseudo-random design was unable to predict crack velocity of the test data set but yielded acceptable predictions for the validation set. Film opacity was well predicted by the pseudo-random design model. The poor predictive ability of the Box-Behnken and central composite models was attributed to poor interpolation of the high curvature of the response surfaces. In contrast, the pseudo-random design mapped the interior of the design space allowing improved interpolation and predictive ability. It is concluded that Box-Behnken and central composite experimental designs are inappropriate for ANN modeling of highly curved responses and that extensive internal mapping of the design space is essential to generate predictive ANN models.
Pharmaceutical and Analytical R&D, AstraZeneca R&D Charnwood, Bakewell Road, Leicestershire LE11 5RH, Loughborough, UK. phil.plumb@astrazeneca.com
A Philip
AP
Plumb
Raymond C
RC
Rowe
Peter
P
York
Christopher
C
Doherty
D015195:Drug Design; D004355:Drug Stability; D008956:Models, Chemical; D016571:Neural Networks, Computer; D013608:Tablets, Enteric-Coated / Q000737:chemistry*
D013608:Tablets, Enteric-Coated