Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate

Pharm Dev Technol. 2017 Nov;22(7):851-859. doi: 10.3109/10837450.2015.1089898. Epub 2015 Sep 24.

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.

Keywords: Controlled-release; IVIVC; experimental design; indapamide; matrices.

MeSH terms

  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations*
  • Drug Compounding
  • Indapamide*
  • Tablets

Substances

  • Delayed-Action Preparations
  • Tablets
  • Indapamide