title: Combined effect of SLS and (SBE)(7M)-beta-CD on the solubilization of NSC-639829.
abstract: Complexation and micellization are two effective ways of solubilizing drugs. In this study, the combined effect of surfactant and complexant on the solubilization of a poorly water soluble compound (NSC-639829) is investigated. With increasing concentration of sodium lauryl sulphate (SLS) in solutions of fixed concentration of (SBE)(7M)-beta-CD, the total solubility of the drug decreases linearly, reaches a minimum and then increases linearly. At each minimum, the molar ratio of SLS to (SBE)(7M)-beta-CD is close to unity. The above observation is attributed to the fact that the surfactant molecule competes with the drug to "fit" in the non-polar cyclodextrin cavity. The surfactant depletes cyclodextrin to form a 1:1 complex. Once the concentration of free SLS reaches the CMC, it starts forming micelles and hence, solubilizes the drug. A slight decrease of the solubilizing power is noticed in the presence of SLS/(SBE)(7M)-beta-CD complex. The combined use of two solubilizing agents, a surfactant and a complexant, results in a much lower solubility than when either one is used alone at the same concentration. The surfactant molecule acts as a competitive inhibitor in the solubilization of the drug by the complexant. Similarly the complexant "pulls" the surfactant out of solution, making it unavailable for solubilizing the drug.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, 1703 E. Mabel Street, Tucson, AZ 85721, USA. yang@pharmacy.arizona.edu
authors.forename: Gang
authors.initials: G
authors.lastname: Yang
authors.forename: Neera
authors.initials: N
authors.lastname: Jain
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Yalkowsky
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D004339:Drug Compounding; D011743:Pyrimidines / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry*; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; C434925:N-4-((5-bromo-2-pyrimidoxy)-3-methylphenyl)-(2-dimethylamino)benzoylurea; D011743:Pyrimidines; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D012967:Sodium Dodecyl Sulfate; D014508:Urea