Alternative matrix formers for nanosuspension solidification: Dissolution performance and X-ray microanalysis as an evaluation tool for powder dispersion

Eur J Pharm Sci. 2008 Nov 15;35(4):344-53. doi: 10.1016/j.ejps.2008.08.003. Epub 2008 Aug 14.

Abstract

Four alternative matrix formers [Avicel PH101, Fujicalin (CaHPO(4)), Aerosil 200 (SiO(2)) and Inutec SP1] were evaluated for their capability in preserving rapid dissolution after spray-drying of nanosuspensions. Model drug compounds selected were cinnarizine (CIN), itraconazole (ITR) and phenylbutazone (PHB) as they showed a decrease in dissolution rate upon spray-drying in the absence of additional matrix formers, yielding release values after 5min of dissolution (release(5min)) of 57.7+/-1.0% (CIN), 56.3+/-3.8% (ITR) and 67.4+/-1.3% (PHB). Compared to the situation without matrix former inclusion, the performance of Avicel PH101 was good for CIN (release(5min)=90.9+/-7.7%), intermediate for PHB (release(5min)=81.0+/-6.4%) and poor for ITR (release(5min)=42.1+/-4.2%). For Fujicalin, intermediate (PHB: release(5min)=87.7+/-3.0%) or poor (CIN: release(5min)=66.1+/-3.4%; ITR: release(5min)=55.9+/-5.2%) performance was seen. Results for Aerosil 200 were good for all compounds (CIN: release(5min)=91.5+/-2.5%; ITR: release(5min)=83.8+/-3.4%; PHB: release(5min)=95.5+/-2.4%), indicating that the large specific surface area was in this case translated into good matrix forming capabilities. Finally, the best results were obtained for Inutec SP1 (CIN: release(5min)=88.7+/-1.2%; ITR: release(5min)=93.4+/-2.4%; PHB: release(5min)=101.3+/-4.9%). Except for Avicel PH101, Cl-maps from X-ray microanalysis of the itraconazole powders supported the hypothesis that better dispersion of drug in the powders results in faster dissolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemistry
  • Chromatography, High Pressure Liquid
  • Desiccation
  • Drug Compounding
  • Electron Probe Microanalysis
  • Excipients / chemistry*
  • Itraconazole / administration & dosage
  • Itraconazole / chemistry
  • Light
  • Microscopy, Electron, Scanning
  • Nanoparticles
  • Particle Size
  • Powders / chemistry*
  • Scattering, Radiation
  • Solubility
  • Suspensions / chemistry*

Substances

  • Antifungal Agents
  • Excipients
  • Powders
  • Suspensions
  • Itraconazole