ABSTRACT
CONTEXT: Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. OBJECTIVE: Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. MATERIALS AND METHODS: In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. RESULTS: The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. CONCLUSIONS: The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.
