Solubilization of cyclosporin A.
This study investigated the solubilization of cyclosporin A (CsA), a neutral undecapeptide, by cosolvency, micellization, and complexation. Cosolvents (ethanol, propylene glycol, polyethylene glycol, tetrahydrofurfuryl alcohol polyethyleneglycol ether, and glycerin), surfactants (polyoxyethylene sorbitan monooleate [(Tween 80)], polyoxyethylene sorbitan monolaurate [(Tween 20)], and Cremophor EL), and cyclodextrins (alpha-cyclodextrin [(alphaCD)] and hydroxypropyl-beta-cyclodextrin[(HPbetaCD)] were used as solubilizing agents in this study. Surfactants had a noticeable effect in increasing CsA solubility. Twenty percent solutions of Tween 20, Tween 80, and Cremophor EL increased the solubility by 60 to 160 fold. Cyclodextrins can increase the CsA solubility, but alphaCD was more effective than HPbetaCD. Cosolvents on the other hand did not increase the solubility of CsA as much as expected from the LOGP (logarithm of water-octanol partition coefficient) value of CsA.
Ran
Y
Y
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA. ran@pharmacy.arizona.edu
Zhao
L
L
Xu
Q
Q
Yalkowsky
S H
SH
D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry; D016572:Cyclosporine / Q000737:chemistry*; D004355:Drug Stability; D008823:Micelles; D008956:Models, Chemical; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry
D003505:Cyclodextrins; D008823:Micelles; D012996:Solutions; D012997:Solvents; D013501:Surface-Active Agents; D016572:Cyclosporine