Planta Med 2007; 73 - P_262
DOI: 10.1055/s-2007-987043

Nanosystems with taxifolin for solid dosage form and its bioavailability in vitro

I Urakova 1, O Pozharitskaya 1, A Shikov 1, V Makarov 1, V Tikhonov 2
  • 1St-Petersburg Institute of Pharmacy, 27–424, Partizanskaya str., 195248, St.-Petersburg, Russia
  • 2“Diod“ Ltd, 11
  • aDerbenevskaya ave., 113114, Moscow, Russia

Flavonoids are naturally-occurring substances possessing some positive effects on human health. Taxifolin is widely distributed in the rind of Siberian and Dahurian larchs. In recent years taxifolin has shown capillaryprotective, anti-inflammatory, antioxidant, and hepatoprotective activities [1–3]. Flavonoids are slightly soluble in water and show a slow dissolution rate from solid oral forms, restricting their use in therapy. It is well known that the drug dissolution rate can be the critical limiting step in the bioavailability after oral administration and the therapeutic effect of the drug. The aim of this work was to increase the dissolution rate of taxifolin. Nanosystems with taxifolin were formed by solid dispersion polymers: polyethylene glycol 6000 (PEG) and Kollidone 17PF (PVP).

Solid dispersions of taxifolin (SDT) were prepared in different ratios of drug:carrier (1:5; 1:7; 1:10; 1:13, w/w) by using melting (PEG) and solvent (PVP) methods. The differential scanning calorimetry (DSC) and microscopy data were applied to estimate the physical state and interactions of taxifolin with polymers. The dissolution tests of SDT were performed according to the basket method. Water, simulated gastric (pH 1.2) and intestinal (pH 6.8) liquids were dissolution medium.

The DSC and microscopy data have shown that in solid dispersion systems a crystal structure of pure taxifolin is not determined. In SDT there was a considerable enhancement in the dissolution rates of taxifolin in comparison with the pure compound. The best bioavailability in vitro of taxifolin were obtained from SDT with 1:10 drug:carrier ratio. The values of dissolution constants determined by first order model for SDT dissolution were markedly higher than for pure drug dissolution in all dissolution media. The constants of rate release of SDT (PVP), SDT (PEG) and taxifolin in water were 0.0819±0.004min-1, 0.0398±0.002min-1 and 0.0097±0.001min-1, respectively.

It was established that polymer nature and its ratio with taxifolin allow to develop nanosystems with controlled release.

References: [1] Habtemariam et al. (1997) J. Nat. Prod. 60: 775–778. [2] Nielsen et al. (1998) Xenobiot. 28: 389–401. [3] Teselkin et al. (2000) Phytother. Res. 14: 160–162.