Agglomerates containing pantoprazole microparticles: modulating the drug release

AAPS PharmSciTech. 2009;10(2):335-45. doi: 10.1208/s12249-009-9214-5. Epub 2009 Mar 25.

Abstract

Pantoprazole-loaded microparticles were prepared using a blend of Eudragit S100 and Methocel F4M. The accelerated stability was carried out during 6 months at 40 degrees C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5-79.0%), drug loading (58-101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm(-2)), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage
  • 2-Pyridinylmethylsulfinylbenzimidazoles / chemistry*
  • Anti-Ulcer Agents / chemistry*
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Drug Stability
  • Lecithins / chemistry
  • Mannitol / chemistry
  • Methylcellulose / administration & dosage
  • Methylcellulose / chemistry
  • Microscopy, Electron, Scanning
  • Pantoprazole
  • Polymethacrylic Acids / administration & dosage
  • Polymethacrylic Acids / chemistry
  • Powders
  • Solubility
  • Technology, Pharmaceutical*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Delayed-Action Preparations
  • Lecithins
  • Polymethacrylic Acids
  • Powders
  • methylmethacrylate-methacrylic acid copolymer
  • Mannitol
  • Methylcellulose
  • Pantoprazole