Enhanced water solubility and stability of curcumin by microinclusion in natural and semi-synthetic cyclodextrins

Curcumin is a natural polyphenolic constituent of Curcuma longa L. It has been generally associated with a large number of biological activities, including anti-oxidant, anti-inflammatory [1] and anti-cancer [2] properties. Although curcumin is a safe molecule even at high doses, its therapeutic use is limited by its low hydro-solubility in acid or physiological pH [3] and, consequently, by its poor bioavailability. Another drawback for clinical application of curcumin is its rapid hydrolysis under alkaline conditions and its photochemical degradation. The overall aim of this project is to increase solubility and stability of curcumin by microinclusion in cyclodextrins.

Solubility studies of curcumin in presence of different concentrations of natural (α, β, γ) and semi-synthetic cyclodextrins (HEβ, DMβ, TMβ, RAMEB, HPβ, HPγ) were carried at different temperatures (25–37°C). Thermodynamic parameters related to complex formation (ΔG, ΔH and ΔS) were also evaluated. Stoichiometry of curcumin inclusion and apparent equilibrium constants (K1, K2) were evaluated by Job's plot method using UV detection. Inclusion of curcumin into selected cyclodextrins was obtained by co-fusion, co-lyophilization, co-evaporation and physical mixture. Complex characterization was achieved by DSC, UV, NMR and HPLC/DAD analysis. Between the cyclodextrins tested the most efficient in order to maximise curcumin solubilisation was DMβ and the most effective complexation technique was the co-lyophilization. This latter was then employed, after curcumin complexation, for the realization of a topical formulation, useful as local anti-inflammatory medicament, and pharmacokinetic was evaluated by in vitro test using Franz cells apparatus.

References: 1. Dong-Oh M (2008) Bioch Bioph Res Comm 375: 275–279

2. Preetha A et al. (2008) Cancer Lett 267: 133–164

3. Tonnesen HH et al. (2002) Int J Pharm 244: 127–135.