Investigation of curcumin-cyclodextrin inclusion complexation in aqueous solutions containing various alcoholic co-solvents and alginates using an UV-VIS titration method. Studies of curcumin and curcuminoides, XXXV.
The effect of pharmaceutical excipients like alcoholic co-solvents and water-soluble polymers on the inclusion complexation of curcumin in hydroxypropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin was investigated with a UV-VIS titration method. The association constants and the stoichiometries of the inclusion complexes in buffered media containing various amounts dl of alcoholic co-solvents and alginates were determined. The results showed a 1 : 1 stoichiometry between curcumin and both the cyclodextrins investigated in buffered media containing 10% (v/v) alcoholic co-solvents, although some 1 : 2 (host:guest) complexation was suspected between curcumin and hydroxypropyl-beta-cyclodextrin. The presence of 0.1% (w/v) sodium alginate or propylene glycol alginate did apparently not change the stoichiometry of the complexes formed. Curcumin was found to have a more than 30-fold higher association constant with hydroxypropyl-gamma-cyclodextrin compared to hydroxypropyl-beta-cyclodextrin in buffer containing 0.5% ethanol. Large variation in the association constants between curcumin and the cyclodextrins as a result of different co-solvents in the aqueous complexing media were found. A decrease in the association constant was seen as the chain lenght of the added co-solvent increased. Further, a decrease in the association constants was observed by addition of alginates in the case of hydroxypropyl-gamma-cyclodextrin at 0.5 or 5% (v/v) ethanol. The trend was opposite in the case of hydroxypropyl-beta-cyclodextrin, where a 30-90% increase in the association constant was observed in the presence of alginates. The results in the current study showed the large variations in the complexation between curcumin and hydroxypropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin, resepctively, as a result of various alcoholic co-solvents and alginates in the complexing media. The results also illustrated the importance of optimizing the solvent systems when utilizing cyclodextrins as drug carriers.
Hegge
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AB
School of Pharmacy, Department of Pharmaceutics, University of Oslo, P.O. 1068 Blindern, 0316 Oslo, Norway. a.b.hegge@farmasi.uio.no
Másson
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M
Kristensen
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Tønnesen
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HH
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000438:Alcohols / Q000737:chemistry*; D000464:Alginates / Q000737:chemistry*; D003474:Curcumin / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D005079:Excipients; D005990:Glycerol / Q000737:chemistry; D019999:Pharmaceutical Solutions; D011092:Polyethylene Glycols / Q000737:chemistry; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins
D000438:Alcohols; D000464:Alginates; D003505:Cyclodextrins; D005079:Excipients; D019999:Pharmaceutical Solutions; D012997:Solvents; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols; D003474:Curcumin; D005990:Glycerol