pH-dependent release of platycodin mitigates its gastrointestinal mucosa irritation after oral administration in rats.

The present study aimed to evaluate the gastrointestinal mucosa irritation of three platycodin formulations. Platycodin-loaded core pellets were prepared via extrusion-spheronization method and coated with Eudragit(®) L100-55 (L100) or Eudragit(®) S100 (S100) for pH-dependent release. The release of platycodin D from coated pellets exhibited pH dependent release profiles. The pharmacokinetic study in rats showed that Tmax of the coated pellets were prolonged as compared to that of un-coated pellets. The S100-coated pellets possess a lower Cmax and decreased AUC0-24h as compared to the L100-coated and uncoated pellets. Hematoxylin-eosin staining and nuclear factor Kappa B (NF-κB) measurement were carried out to observe the gastrointestinal mucosa irritations. The results revealed that the irritations of platycodin on the upper gastrointestinal mucosa are dose-dependent. However, no obvious irritation effect on the gastrointestinal tissues of rats was detected after oral administration of the coated pellets. In addition, the amount of NF-κB in the stomach of rats treated with the uncoated pellets was about fivefold higher as compared to that of the coated pellets. In summary, the L100-coated platycodin pellets exhibited higher oral bioavailability and less gastrointestinal mucosa irritations as compared to the other two formulations.