Preparation and optimization of glyceryl behenate-based highly porous pellets containing cilostazol

Pharm Dev Technol. 2018 Jun;23(5):540-551. doi: 10.1080/10837450.2016.1245743. Epub 2016 Nov 3.

Abstract

The aim of this study was to prepare a highly porous multiparticulate dosage form containing cilostazol for gastroretentive drug delivery. The floating pellets were prepared with glyceryl behenate as a matrix former and camphor as a sublimating agent by extrusion/spheronization and sublimation under vacuum. Granules prepared with sublimation at 60 °C displayed a slower dissolution rate and smoother surface morphology than those prepared at lower temperatures. This was unexpected as the reported melting point of glyceryl behenate is higher than 69 °C. The DSC study revealed that melting began at a lower temperature owing to the multicomponent property of glyceryl behenate, which led to a sintering effect. The prepared pellets were spherical with unimodal size distribution. They also had porous structures with increased porosity, which led to immediate buoyancy. As cilostazol is a hydrophobic drug that has an erosion-based release mechanism, drug release profile was highly correlated with the percentage of disintegrated pellets. Various excipients were added to the glyceryl behenate-based formulation to increase the floating duration. When hydroxyethyl cellulose was added to the glyceryl behenate-based pellets, acceptable dissolution rate and buoyancy were acquired. This system could potentially be used for gastroretentive delivery of various hydrophobic drugs, which was generally considered difficult.

Keywords: Floating; cilostazol; gastroretentive; glyceryl behenate; porous; sintering.

MeSH terms

  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / chemistry
  • Cilostazol
  • Desiccation
  • Drug Compounding
  • Drug Delivery Systems
  • Drug Liberation
  • Excipients / chemistry*
  • Fatty Acids / chemistry*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / chemistry
  • Porosity
  • Solubility
  • Tablets
  • Tetrazoles / administration & dosage*
  • Tetrazoles / chemistry

Substances

  • Bronchodilator Agents
  • Excipients
  • Fatty Acids
  • Platelet Aggregation Inhibitors
  • Tablets
  • Tetrazoles
  • glyceryl behenate
  • Cilostazol