ABSTRACT
OBJECTIVE: To discuss whether the difference in dissolution profile in vitro may cause different bioavailability in vivo and investigate the effects of the key quality parameters of leflunomide on bioavailability. METHODS: Using SANOFI product as the reference preparation and domestic product as the test preparation, the disintegration solution of leflunomide tablets was analyze by Morphologi G3-ID automated measurement to get the paricile size and size distribution of the API; using pH 6.5 FaSSIF solution without adding ox-gall sulfonic acid sodium and lecithin as the dissolution medium, the dissolution and permeation profiles of the reference and test preparations and raw material were compared at 37 ℃ with rotate speed of 150 r•min-1. The influence of quality parameters on the process of API's release and absorption was investigated, then the difference between the reference and test preparations were compared to preliminarily predict the bioavailability and bioequivalence. RESULTS: The particle size Dv(50)of domestic leflunomide tablets was 79.80 μm, while the particle size Dv(50)of the reference product was 17.60 μm; the dissolution rate and penetration rate of the test preparation were about 70% of the reference preparation, the tmax was basically identical,but the ρmax and AUC0-t were lower than the reference preparation. The bioavailability of the test preparation was about 90% of the reference preparation. CONCLUSION: Though the dissolution profile of domestic leflunomide tablets is not identical to the reference preparation, but the two products were predicted to be bioequivalent.
ABSTRACT
The present study was designed to investigate the non-alkaloid compounds from the leaves and stems of Vinca major cultivated in Yunnan Province, China. The compounds were isolated using chromatographic techniques. The structures were elucidated by 1D- and 2D-NMR spectroscopic methods in combination with UV, IR, and MS analyses. The 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging activity of Compounds 1-7 were evaluated. One new iridoid glycoside (compound 1), together with 11 known compounds, were isolated from Vinca major. Compounds 1, 5, and 6 showed moderate DPPH-scavenging activity, with IC50 values being 70.6, 32.8, and 62.2 μmol·L(-1), respectively. In conclusion, compound 1 is a newly identified iridoid glycoside with moderate antioxidant activity.