ABSTRACT
Objective To establish assay methods for the determination of dissolution,content and related substances of vita-min K1 self-nanoemulsifying drug delivery system(VK1-SNEDDS),and investigate the physico-chemical properties of the preparation. Methods The UV method was established to determine the dissolution of VK1-SNEDDS. The content and related substances were de-termined by HPLC. The appearance,self-emulsification time,micro-morphology,droplet size and zeta potential were also investigat-ed. Results The linearity range of established UV and HPLC methods was 0.85-20.4 and 2.16-216μg/ml,respectively,and all the recovery,precision,specificity and sensitivity met requirements. VK1-SNEDDS could disperse quickly after dilution. The transmission electron microscope(TEM)image of the optimized liquid SNEDDS showed that most of the emulsion droplets were of uniform size with no signs of coalescence. Droplet size of optimal formulation was revealed as 47.74 nm with polydispersibility index(PDI)of 0.248,and zeta potential was found to be-20.53 mV. Conclusion VK1-SNEDDS could form homogeneous and stable nanoemulsion when dilut-ed with aqueous phase and increase the dissolution of lipophilic drug. The methods are reliable,accurate and suitable for quality con-trol of VK1-SNEDDS.
ABSTRACT
OBJECTIVE: To investigate the differences of two matrine (MA) self-nanoemulsifying drug delivery systems (SNEDDS) in intestinal lymphatic transport. METHODS: Triple single pass intestinal perfusion model (T-SPIP) was established to study the intestinal absorption kinetics of MA in different absorption segments of rats with chylomicron flow blocking approach using colchicine as the blocker. The concentration of MA in the perfustae was measured by HPLC. RESULTS: The two SNEDDSs had regular spherical surface and narrow particle size distribution. MA showed high Peff. The phospholipid complex formulation (MPC-SN) exhibited higher intestinal lymphatic transport especially in distal ileum, and it was influenced more significantly by the chylomicron flow blocker in distal ileum compared to in proximal jejunum and mid-small intestine. CONCLUSION: SNEDDS can improve the absorption of MA by intestinal lymphatic transport. MPC-SN might be easier to be absorbed via lymphatic transport because of its high lipophilicity and small particle size.
ABSTRACT
Objective of present study was to prepare and characterize self-nanoemulsifying drug delivery system (SNEDDS) of lutein and to evaluate its effect on bioavailability of warfarin. The SNEDDS was prepared using an oil, a surfactant, and co-surfactants with optimal composition based on pseudo-ternary phase diagram. Effect of the SNEDDS on the bioavailability of warfarin was performed using Sprague Dawley rats. Lutein was successfully formulated as SNEDDS for immediate self-emulsification and dissolution by using combination of Peceol as oil, Labrasol as surfactant, and Transcutol-HP or Lutrol-E400 as co-surfactant. Almost complete dissolution was achieved after 15 min while lutein was not detectable from the lutein powder or intra-capsule content of a commercial formulation. SNEDDS formulation of lutein affected bioavailability of warfarin, showing about 10% increase in Cmax and AUC of the drug in rats while lutein as non-SNEDDS did not alter these parameters. Although exact mechanism is not yet elucidated, it appears that surfactant and co-surfactant used for SNEDDS formulation caused disturbance in the anatomy of small intestinal microvilli, leading to permeability change of the mucosal membrane. Based on this finding, it is suggested that drugs with narrow therapeutic range such as warfarin be administered with caution to avoid undesirable drug interaction due to large amount of surfactants contained in SNEDDS.