Establishing and analyzing the design space in the development of direct compression formulations by gene expression programming.
OBJECTIVE
In this paper we have evaluated the gene expression programming (GEP) methodology for modeling the effect of different variables (continuous and nominal) and their interactions on the properties of direct compression formulations.


METHODS
The effect of four variables was studied; variety of diluents, type and percentage of drug and maximum compression force, on the mechanical and drug release properties of direct compression tablets. The generated database (36 formulations) was used for mathematical and GEP modeling.


RESULTS
GEP has been shown to have a high accuracy in prediction for four out five outputs studied including friability which had no replicate measurements. Compared to the traditional statistical treatment GEP is less time consuming and gives equations which are extremely helpful in understanding the interactions of the different variables and for establishing the design space in the development of direct compression formulations.


CONCLUSIONS
GEP allows similar conclusions than traditional statistical treatment. The helpfulness of this methodology in establishing the design space has been demonstrated. The knowledge derived from GEP can easily be increased by including additional information or new inputs, such as additional drugs or combinations of excipients in the data set.
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Campus Vida, Universidad de Santiago de Compostela, Santiago de Compostela, Spain. m.landin@usc.es
Mariana
M
Landin
Raymond C
RC
Rowe
Peter
P
York
D000465:Algorithms; D003198:Computer Simulation; D016208:Databases, Factual; D004339:Drug Compounding / Q000379:methods*; D015195:Drug Design; D005079:Excipients / Q000737:chemistry; D015233:Models, Statistical; D008962:Models, Theoretical; D013607:Tablets; D013997:Time Factors
D005079:Excipients; D013607:Tablets