[Preparation, characterization and antitumor of cyclodextrin inclusion of an anti-cancer drug regorafenib].

Objective: In order to improve the drug's solubility, dissolution and bioavailability, RG-ß-CD, RG-γ-CD and RG-Hp-ß-CD were prepared by co-crystallization between Regorafenib (RG) and ß-cyclodextrin (ß-CD), γ-cyclodextrin (γ-CD) and Hydroxypropyl-ß-cyclodextrin (Hp-ß-CD). Methods: Three inclusion complexes were prepared by recrystallization and solvent evaporation methods and characterized by fourier transform infrared spectroscopy (FT-IR), thermal analysis (TG), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), 1H nuclear magnetic resonance (1H-NMR), nuclear overhauser effect spectroscopy (NOESY). In vivo experiments, tumor suppression assay were made with SW620 colon cancer cell. Results: The ability of solubility and dissolution were improved after inclusion with three kinds of cyclodextrins. The regorafenib-ß-cyclodextrin inclusionis proved to have the best stability. The less enhanced was regorafenib-γ-cycl-odextrin inclusion. The best dissolution of regorafenib-ß-cyclodextrin inclusion complex was to bring as the tumor suppression assay, the result shows that regorafenib inclusion with ß-cyclodextrin is better than regorafenib itself. Conclusion: The bioavailability of regorafenib by inclusion with cyclodextrin can enhance due to the solubility enhancement of RG, which can provide an effective method for improving solubility and dissolution of insoluble drug in clinical medication.

[Characterization and stability of S (-) pantoprazole sodium hydrates].

Objective: To study the characteristics and stability of new S(-) pantoprazole sodium hydrates. Methods: The X-ray single crystal diffractometer (SXRD), X-ray powder diffractometer (PXRD), thermogravimetric analysis (TG) and infrared spectrometry (IR) were used to characterize S(-) pantoprazole sodium hydrates. The stability of the hydrates was evaluated by high temperature test,affecting factors test and accelerated test. Results: The crystalline water in S(-) pantoprazole sodium hydrates were very easy to lose and obtain, but crystal structure was not changed significantly. The transition from S(-) pantoprazole sodium trihydrate to S(-) pantoprazole sodium hemipentahydrate occurred at approximately 40 ℃ and reversible transitions from hemipentahydrate to trihydrate occurred at high humidity. Two hydrates had no significant difference in accelerated test. Conclusion: The crystal structure of the two hydrates are almost the same, hemipentahydrate is more stable than trihydrates at high temperature or at exposure to light(at 4500 ± 500 lx).

[Synthesis, characterization and antitumor activity of 5-fluorouracil-nicotinamide cocrystal].

Objective: To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. Methods: The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. Results: According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 µg/mL and 42.6 µg/mL, respectively. Conclusion: 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.