title: Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: a Research & Development, ALKALOID AD , Skopje , Republic of Macedonia.
authors.forename: Packa
authors.initials: P
authors.lastname: Antovska
authors.affiliation: a Research & Development, ALKALOID AD , Skopje , Republic of Macedonia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Ugarkovic
authors.affiliation: a Research & Development, ALKALOID AD , Skopje , Republic of Macedonia.
authors.forename: Gjorgji
authors.initials: G
authors.lastname: Petruševski
authors.affiliation: a Research & Development, ALKALOID AD , Skopje , Republic of Macedonia.
authors.forename: Bosilka
authors.initials: B
authors.lastname: Stefanova
authors.affiliation: a Research & Development, ALKALOID AD , Skopje , Republic of Macedonia.
authors.forename: Blagica
authors.initials: B
authors.lastname: Manchevska
authors.affiliation: b Department of Inorganic Chemistry, Faculty of Pharmacy , Institute of Applied Chemistry and Pharmaceutical Analyses, SS Cyril and Methodius University , Skopje , Republic of Macedonia , and.
authors.forename: Rumenka
authors.initials: R
authors.lastname: Petkovska
authors.affiliation: c Institute of Chemistry, Faculty of Natural Sciences and Mathematics, SS Cyril and Methodius University , Skopje , Republic of Macedonia.
authors.forename: Petre
authors.initials: P
authors.lastname: Makreski
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D007190:Indapamide; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D007190:Indapamide
keywords: Controlled-release; IVIVC; experimental design; indapamide; matrices