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Kava & Beta cyclodextrin to increase oral bioavailability

Discussion in 'New Members Forum' started by VictoriousSpoon, Jan 14, 2020.

  1. According to a 2010 Italian study (1), beta cyclodextrin* effectively doubled the water solubility of (S)-7,8-dihydrokavain, one of the primary anxiolytic kavalactones. While only one kavalactone was studied here, this should work similarly with all semi polar-lipophyllic kavalactones. Cyclodextrins have been used for over two decades to increase bioavailability of various drugs and supplements that have poor water solubility.

    Has anyone experimented with this combo? Do share your experience please.
    Added to the bucket list.

    *Beta cyclodextrin is a ring-shaped sugar molecule, that has lipophyllic interiors, and hydrophillic exteriors and can effectively be used to encapsulate non-water loving molecules in aqueous solutions, to dramatically enhance absorption efficiency when ingested.

    (1) J Pharm Biomed Anal. 2010 Aug 1;52(4):479-83. doi: 10.1016/j.jpba.2010.01.037. Epub 2010 Feb 1.
    Cyclodextrins as carriers for kavalactones in aqueous media: spectroscopic characterization of (S)-7,8-dihydrokavain and beta-cyclodextrin inclusion complex.
    Pescitelli G1, Bilia AR, Bergonzi MC, Vincieri FF, Di Bari L.
    Author information
    University of Pisa, Department of Chemistry and Industrial Chemistry, via Risorgimento 35, 56126 Pisa, Italy.
    Kavalactones represent the active constituents of kava-kava (Piper methysticum G. Forster), endowed with sedative and anaesthetic properties. Kavalactones are polar constituents, but poorly soluble in water with a low bioavailability. In this study, the formation of inclusion complexes of one of the most representative kavalactone isolated from kava-kava extract, (S)-7,8-dihydrokavain (DHK), with beta-cyclodextrin (beta-CyD) was investigated mainly by spectroscopic methods. NMR experiments were extensively used for the complete characterization of the complex and included (1)H NMR complexation shifts analysis, (1)H NMR diffusion measurements (DOSY), and ROESY experiments. In particular DOSY experiments demonstrated that in the presence of beta-CyD the translational diffusion of kavalactone is sizably slowed down (2.5x10(-10)m(2)/s) with respect to the free drug (4.4x10(-10)m(2)/s) according to the inclusion of DHK in the cavity of (beta-CyD). ROESY experiments confirmed the inclusion of DHK in the hydrophobic pocket of beta-CyD through the primary hydroxyl rim, being the most relevant interactions between the H3' of beta-CyD and the ortho protons on the phenyl ring of the DHK, and between H5' of beta-CyD and the meta/para protons of DHK phenyl ring. The inclusion of the phenyl ring of DHK, leaving the lactone moiety outside of CyD was also confirmed by the induced CD effects. The binary solution DHK/beta-CyD shows a 50% intensity increase of the negative band of the pi-pi* transitions of the phenyl ring with respect to the absorption observed with DHK alone. Molecular dynamics simulations results corroborated and further clarify observed spectroscopic data. It was found that the phenylethyl substituent at C6 has a preferential equatorial position in the free state, and an axial one in the complex, justifying the large downfield shift experienced by H6 of DHK upon binding. Finally the influence of beta-CyD on water solubility of DHK was investigated by phase-solubility studies. In the range 2-4mM of host, solubility of DHK was increased only two-fold, but being beta-CyD also a penetration enhancer, in vivo studies will be performed to clarify a possible role of the complex on the bioavailability of DHK.

    Copyright (c) 2010 Elsevier B.V. All rights reserved.




    Last edited: Jan 14, 2020
    Mo'iety and JohnMichael like this.
  2. Zaphod

    Zaphod Kava Enthusiast

  3. Mo'iety

    Mo'iety Kava Enthusiast

    This is definitely interesting. I imagine it'd be like lecithin and other emulsifiers, in theory they can increase the strength of prepared grog by holding more kavalactones in solution. But kava is a suspension anyway - a supersaturated mix of kava particulate matter with way more kavalactones than could actually be held in solution. Some people swear by lecithins in their prep, but most find that there's no improvement over plain water.

    The most interesting thing would be how the beta-CyD influences uptake in the gut. It's quite possible it could be like fatty foods and help the kavalactones get more rapidly absorbed, thus strengthening the experience. Or maybe it has no effect at all. Sounds like we need a guinea pig :)

    Edit: Also, @mods we should consider moving this thread to the In-Depth Kava Discussion
    VictoriousSpoon likes this.

  4. I've tried lecithin- it seems to help modestly, but definitely not a two-fold increase. Lecithin isn't water soluble itself, so I do think the ß Cyclodextrin may offer superior results, since hydrophillic compounds (like alcohol) can be absorbed in the gut and large intestine (in addition to small intestine), whereas lipophillic compounds tend to be strictly absorbed in the small intestine.
    Mo'iety likes this.
  5. I actually tried to make this thread there first, but my post count forbids me.