betadex and genipin

Complexes of Genipin and different water-soluble adjuvant polysaccharides, such as arabinogalactane, hydroxyethyl starch, fibergum, and oligosaccharides β-CD and HP-β-CD, were synthesized as drug delivery system using mechanochemical technology.. We have investigated physicochemical properties, stability, and hepatotoxicity of the synthesized complexes in solid state and aqueous solution. The formation of the complexes was evidenced by different physical and spectroscopy assays, and the stability constants of our synthesized Genipin-based complexes were also calculated.. The HP-β-CD inclusion complex showed the highest characteristics. We have found that the molecule of Genipin was completely included in the cyclodextrin cavity of the HP-β-CD. This complex of Genipin has shown a 6.14-fold increase of solubility compared with the original Genipin, and more stable in solvent and solid states.. The hepatotoxicity assays showed that our investigated complexes of Genipin are much safer than the original Genipin. These results suggest that new Genipin-based preparations can be synthesized with advantageous of higher stability and safety.

Topics: beta-Cyclodextrins; Cell Survival; Cholagogues and Choleretics; Drug Compounding; Drug Delivery Systems; Drug Liberation; Drug Stability; Hep G2 Cells; Humans; Hydroxyethyl Starch Derivatives; Iridoids; Solubility

The purpose of this work is to investigate the effect of the genipin/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the intestinal absorption of genipin and identify its mechanism of action. The phase solubility profile was classified as A(L) type, indicating the formulation of a 1:1 stoichiometry inclusion complex. Fourier transform infrared spectroscopy, Differential scanning calorimetry, X-ray powder diffractometry, and (1)H nuclear magnetic resonance (NMR) and two-dimensional (2D) (1)H rotating-frame Overhauser enhancement (ROESY) NMR spectroscopies further confirmed the formulation of the inclusion complex with superior dissolution properties than the drug alone. The results of single-pass intestinal perfusion showed that the intestinal absorption of genipin was affected by P-glycoprotein (Pgp). The absorption rate and permeability value of the inclusion complex were significantly higher than the free drug, suggesting that its enhancing effect was involved in its solubilizing effect and Pgp inhibitory effect. The mechanisms of HP-β-CD on Pgp inhibition were demonstrated by restraining the Pgp ATPase activity rather than changing the fluidity of the cell membrane.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; beta-Cyclodextrins; Chemistry, Pharmaceutical; Cholagogues and Choleretics; Intestinal Absorption; Iridoid Glycosides; Iridoids; Magnetic Resonance Spectroscopy; Male; Rats; Rats, Sprague-Dawley; Solubility; Spectroscopy, Fourier Transform Infrared

The aim of this study was to prepare the inclusion complex of genipin (GP) and beta-cyclodextrin (beta-CD) with improved stability, solubility, and bioavailability and to study the pharmacokinetics of beta-CD inclusion complex in mice.. Lyophilization was employed in the preparation of the inclusion complex of GP-beta-CD, whose formation was confirmed by infrared, ultraviolet, differential scanning calorimetry, X-ray diffraction, and phase solubility method. Comparative studies on the in vitro solubility and stability and in vivo evaluation of GP in mice were investigated. Liquid-liquid extraction was used for the isolation of GP in the assay of its concentration. After injection in the caudal vein at equal doses of the inclusion complex of free GP, the drug concentration in mice plasma at fixed time after administration was determined by high-performance liquid chromatography method.. The results demonstrated that GP-beta-CD solid powders showed improved stability and solubility in aqueous solution, when comparing with free GP. The results of the in vivo study showed that the inclusion complex of GP-beta-CD exhibited the dissimilar pharmacokinetics from that of free GP after intravenous administration. The inclusion complex of GP-beta-CD displayed longer MRT(0-infinity) and higher AUC(0-infinity) than free GP did.. The relative bioavailability of the inclusion complex of GP-beta-CD to free GP was 305.3%, which demonstrated that GP formulations containing beta-CD significantly increased the bioavailability.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Biological Availability; Calorimetry, Differential Scanning; Drug Carriers; Drug Stability; Freeze Drying; Half-Life; Iridoid Glycosides; Iridoids; Male; Mice; Powder Diffraction; Random Allocation; Solubility; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared