title: Co-solubilization of poorly soluble drugs by micellization and complexation.
abstract: The use of combined approach of surfactants and cyclodextrins in solubilization of poorly soluble drugs has been described in literature. In this report, a mathematical model has been developed to provide the quantitative basis for this approach. First, by way of hypothetical examples and simulations, the influence of various interaction parameters on the phase solubility profile is presented. Additionally, the model results are compared with (a) results reported by Yang et al., with NSC-639829, sodium lauryl sulfate (SLS) and sulfobutyl-ether-beta-cyclodextrin ((SBE)(7M)-beta-CD) and (b) solubility of methylprednisolone, a model poorly soluble drug, in the presence of its water-soluble 'surfactant-like' prodrug, methylprednisolone 21-hemisuccinate, and (SBE)(7M)-beta-CD. The model shows good agreement with experimental data. Furthermore, theoretical simulations show that the combined solubility is less than the sum of the individual solubility values in cyclodextrins and surfactants. Based on the hypothetical case and the two examples, the factors affecting the phase solubility profile in mixed solutions of surfactants and cyclodextrins are presented. Finally, the limitations of the model to explain co-solubilization by surfactants and cyclodextrins are discussed.
authors.affiliation: Biopharmaceutics R&D, Bristol-Myers Squibb Co., NJ 08903, United States. venkatramana.rao@bms.com
authors.forename: Venkatramana M
authors.initials: VM
authors.lastname: Rao
authors.forename: M
authors.initials: M
authors.lastname: Nerurkar
authors.forename: S
authors.initials: S
authors.lastname: Pinnamaneni
authors.forename: F
authors.initials: F
authors.lastname: Rinaldi
authors.forename: K
authors.initials: K
authors.lastname: Raghavan
mesh_terms: D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D008776:Methylprednisolone Hemisuccinate / Q000737:chemistry; D008823:Micelles; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry; D015203:Reproducibility of Results; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D008823:Micelles; C434925:N-4-((5-bromo-2-pyrimidoxy)-3-methylphenyl)-(2-dimethylamino)benzoylurea; D004364:Pharmaceutical Preparations; D011743:Pyrimidines; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D012967:Sodium Dodecyl Sulfate; D008776:Methylprednisolone Hemisuccinate; D014508:Urea