Spray-dried microparticles of glutathione and S-nitrosoglutathione based on Eudragit(®) FS 30D polymer.

OBJECTIVE: In recent years, S-nitrosoglutathione has been proposed for the treatment of Crohn's disease to prevent mucosal barrier failure. In this paper, we report the formulation of spray dried microparticles of glutathione and S-nitrosoglutathione based on Eudragit(®) FS 30D polymer (i.e. colon-specific delivery system).

MATERIAL AND METHODS: The influence of several spray-drying parameters (inlet temperature 80-150°C, solvent flow 5-10mL/min) was studied. The parameters that yielded the best formulations (inlet temperature 120°C, outlet temperature 47°C, solvent flow 5mL/min and air flow 100%) were selected for further studies.

RESULTS: Scanning electron microscopy revealed that the resulting microparticles were spherical in shape. The powder X-ray diffraction patterns of pure GSH and GSNO showed sharp peaks that were not present in the microparticles, confirming a molecular dispersion of the drugs by the polymer. The stability of the drugs in the microparticles was confirmed by Fourier transform infrared spectroscopy. Release studies in phosphate buffer solutions showed fast release at basic pH 7.4, sustained release at pH 6.8, but practically no release at the acidic pHs of 1.2, 3 and 6 for the pH-sensitive microparticles. The microparticles prevented the release of drugs at acidic pH while demonstrating fast release at basic pH 7.4; this suggests the suitability of these microparticles to be evaluated for specific colon targeting.

CONCLUSION: Using Eudragit(®) FS 30D as a gastro-resistant rate-controlling polymer, S-nitrosoglutathion could be targeted to the colon for further studies in the treatment of inflammatory bowel diseases including Crohn's disease.