ABSTRACT
Aim To prepare evodiamine butyryl deriva-tive (EBD) and evodiamine butyryl derivative-loaded solid lipid nanoparticles (EBDLN), and study its re-lease in vitro,and to investigate its in situ gastrointesti-nal absorption. Methods EBD was prepared by a one-step synthetized method, and then EBDLN was prepared by a film dispersion method. Dynamic dialy-sis was used to evaluate drug release in vitro,and sin-gle-pass gastrointestinal perfusion was employed to study the gastrointestinal absorption of EDM,EBD and EBDLN. Results In identical release media, there were identical drug release tendencies of EBD and EB-DLN, but the release rate of EBDLN was faster than EBD. Compared with EDM and EBD, the Kavalues and Pappvalues of EBDLN in every perfusion segment increased significantly. The Kaof EBDLN in stomach, duodenum, jejunum, ileum and colon was 110.14-fold,56.70-fold,51.23-fold,45.70-fold and 127.23-fold of free EDM respectively. The Pappvalue of EB-DLN was 9.74-fold, 4.48-fold, 3.82-fold and 11.3-fold of that of free EDM. Conclusion EBDLN has sustained effect and can enhance the gastrointestinal absorption of EDM and EBD.
ABSTRACT
Objective To investigate the pharmacokinetic behavior and in situ intestinal absorption of evodiamine complex water-in-oil nanoemulation (WECNE). Methods WECNE was formulated with the titration stirring methods. Twelve male SD rats were intragastrically administered with evodiamine (EDA) and WECNE at the same EDA dose of 100 mg • kg-1. Blood samples were collected from eye socket at 0. 083, 0. 25, 0. 5, 0. 75, 1, 2, 5, 8, 12, 24, 48 and 72 h after intragastrical administration, and the plasma concentrations of EDA were determined by RP-HPLC. DAS 2. 1. 1 software was applied to evaluate the pharmacokinetic behavior. Single-pass intestinal perfusion was carried out to test the intestinal absorption in situ. Results The area under the curve (AUC0-72h), peak concentration (Cmax) and time to peak (Tmax) of WECNE were (4 924. 59 ± 1 105. 28) μg • L • h-1, (305. 47 ±51. 23) μg • L-1 and (0. 83 ± 0. 29) h, respectively. The absorption rate constant (Ka) of WECNE in the stomach, duodenum, jejunum, ileum and colon were (1. 05±0. 82)×10-5, (12. 19± 1. 57) × 10-5, (12. 66± 1. 35) × 10-5, (11. 94±4. 17) ×10-5 and (11. 21 ± 1. 25) × 10-5 L • s-1, respectively. In addition, the effective permeability (Peff) of WECNE in the duodenum, jejunum, ileum and colon were (26. 03 ± 3. 84) × 10-5, (18. 48±5. 99) × 10-5, (19. 77 ± 2. 59) × 10-5 and (36. 02±1. 48) × 10-5 cm • s-1, respectively. Conclusion WECNE can improve the bioavailability and the absorption in situ of EDA in different parts of the gastrointestinal tract.