Enhancement of in situ intestinal absorption of an insoluble NO-donating drug ZLR-8 in rats by spray-dried emulsion

Aim ：To explore the in situ intestinal absorption in rats of ZLR-8，an insoluble NO-donor drug，and to compare the intestinal absorption enhancement by spray-dried emulsion. Methods ：Intestine of rats was cannulated for in situ perfusion.UV and HPLC methods were used to monitor phenolsulfonphthalein and ZLR-8， respectively.The effects on ZLR-8 absorption of the intestinal segments，the concentration of ZLR-8 and the pH of the circulating perfusate were studied.The absorption of ZLR-8 suspension was compared to that of the spray-dried emulsion. Results ：1-h in situ intestinal perfusion of the spray-dried emulsion allowed the estimation of the absortion percentage to be (23.54±1.40) %，(15.95±0.09) %，(12.30±0.74) %，(3.98±0.12) %，respectively；the absorption rate constants in duodenum，colon，jejunum and ileum to be (0.248 6±0.046 0) h^-1，(0.143 7±0.036 0) h^-1，(0.069 2±0.001 3) h_{^{-1，(0.020 8±0.000 4) h-1，respectively.Significant differences in absorption characteristics were found among intestinal segments.In the range of 3.4-9.4，pH of the perfuate had significant influence on the absorption of ZLR-8，and better absorption appeared at pH of 5.4 to 7.4.It was found that the absorption rate constant was unaffected by ZLR-8 concentration.However，the absorption amount was proportional to ZLR-8 concentration.Compared to the ZLR-8 suspension，the in situ intestinal absorption of ZLR-8 in rats given the spray-dried emulsion increased significantly. Conclusion ：It was only found that ZLR-8 administered in suspension has minor absorption in rat duodenum while no apparent absorption occurred in other segemnts.ZLR-8 in spray-dried emulsion was fairly absorbed in the rat intestinal segments.Passive diffusion was invloved in the absorption of ZLR-8.Spray-dried emulsion significantly enhanced the intestinal absorption of ZLR-8 in rats.}}