title: Improved aqueous solubility of crystalline astaxanthin (3,3'-dihydroxy-beta, beta-carotene-4,4'-dione) by Captisol (sulfobutyl ether beta-cyclodextrin).
abstract: Carotenoids are the most widely distributed natural pigments, with over 600 individual compounds identified and characterized from natural sources. A few are commercially important molecules, having found utility as additions to animal feed in the aquaculture, poultry, and swine feed industries. The majority are lipophilic molecules with near zero inherent aqueous solubility. Many different methods have been developed to make the carotenoids "water dispersible," as true water solubility has not been described. Astaxanthin (3,3'-dihydroxy-beta, beta-carotene-4,4'-dione) is a commercially important oxygenated carotenoid that has gained wide acceptance as a feed additive in the $50 billion salmon and trout aquaculture industry. Recently, interest in the human health applications of astaxanthin has increased, with astaxanthin receiving approval as a dietary supplement in several countries, including the United States. Moving astaxanthin into a pharmaceutical application will require a chemical delivery system that overcomes the problems with parenteral administration of a highly lipophilic, low molecular weight compound. In the current study, the ability of sulfobutyl ether beta-cyclodextrin (sodium), as the Captisol(R) brand, to increase the aqueous water solubility of crystalline astaxanthin was evaluated. Complexation of crystalline astaxanthin with Captisol increased the apparent water solubility of crystalline astaxanthin approximately 71-fold, to a concentration in the 2 microg/mL range. It is unlikely that this increase in solubility will result in a pharmaceutically acceptable chemical delivery system for humans. However, the increased aqueous solubility of crystalline astaxanthin to the range achieved in the current study will likely find utility in the introduction of crystalline astaxanthin into mammalian cell culture systems that have previously been dependent upon liposomes, or toxic organic solvents, for the introduction of carotenoids into aqueous solution.
authors.affiliation: Hawaii Biotech, Inc., 99-193 Aiea Heights Drive, Suite 200, Aiea, Hawaii 96701, USA. slockwood@hibiotech.com
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Lockwood
authors.forename: Sean
authors.initials: S
authors.lastname: O'Malley
authors.forename: Gerold L
authors.initials: GL
authors.lastname: Mosher
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003505:Cyclodextrins / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D012995:Solubility; D014867:Water; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000737:chemistry*; D047392:beta-Cyclodextrins
chemical_list: D000276:Adjuvants, Immunologic; D003505:Cyclodextrins; D019999:Pharmaceutical Solutions; D024341:Xanthophylls; D047392:beta-Cyclodextrins; D019207:beta Carotene; D014867:Water; C093196:SBE4-beta-cyclodextrin; C005948:astaxanthine