Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies

Drug Dev Ind Pharm. 2010 Feb;36(2):180-9. doi: 10.3109/03639040903468811.

Abstract

Background: Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications.

Method: The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE(R), aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40 degrees C/75% relative humidity] for 3 months.

Results: All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months.

Conclusions: Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage
  • 2-Pyridinylmethylsulfinylbenzimidazoles / chemistry
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Drug Stability
  • Drug Storage
  • Esomeprazole / administration & dosage
  • Esomeprazole / chemistry
  • Excipients / chemistry*
  • Kinetics
  • Lansoprazole
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / chemistry*
  • Solubility
  • Tablets, Enteric-Coated / chemistry

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Delayed-Action Preparations
  • Drug Carriers
  • Excipients
  • Proton Pump Inhibitors
  • Tablets, Enteric-Coated
  • Lansoprazole
  • Esomeprazole