Effect of varying optimization parameters on optimization by guided evolutionary simulated annealing (GESA) using a tablet film coat as an example formulation.
The purpose of this study was to investigate the effect of varying optimization parameters on the proposed optimum of a tablet coating formulation requiring minimization of crack velocity and maximization of film opacity. An artificial neural network (ANN) comprising six input and two output nodes separated by a single hidden layer of five nodes was trained using 100 pseudo-randomly distributed records and optimized by guided evolutionary simulated annealing (GESA). GESA was unable to identify a formulation that satisfied both a crack velocity of 0 ms(-1) and a film opacity of 100% due to conflict centred on the response of the properties to variation in pigment particle size. Constraining film thickness exacerbated the property conflict. By adjusting property weights (i.e. the relative importance of each property), GESA was able to propose formulations that were either crack resistant or that were fully opaque. Reducing the stringency of the performance criteria (crack velocity >0 ms(-1), film opacity <100%) enabled GESA to propose optima that met or exceeded the looser targets. Under these conditions, starting GESA from different locations within model space resulted in the proposal of different optima. Therefore, application of loose targets resulted in the identification of an optimal zone within which all formulations satisfied these less stringent performance criteria. It is concluded that application of the most stringent performance criteria and selection of appropriate property weights is necessary for unequivocal identification of the true optimum. A strategy for optimization experiments is proposed.
Plumb
A Philip
AP
Pharmaceutical and Analytical R&D, AstraZeneca R&D Charnwood, Bakewell Road, Leicestershire LE11 5RH, Loughborough, UK. phil.plumb@astrazeneca.com
Rowe
Raymond C
RC
York
Peter
P
Doherty
Christopher
C
D002626:Chemistry, Pharmaceutical; D016571:Neural Networks, Computer; D013608:Tablets, Enteric-Coated / Q000737:chemistry*
D013608:Tablets, Enteric-Coated