Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility
Zoltán‐István Szabó, G Orban, Enikő Borbás, Dóra Csicsák, Szabina Kádár, Béla Fiser, Máté Dobó, Péter Horváth, Eszter Kiss, Lívia Budai, Judit Dobos, Tamás Pálla, László Őrfi, Gergely Völgyi, Gergő Tóth
Abstract
-type phase-solubility diagram indicated 1:1 stoichiometry in a liquid state. Complementary analytical methods were employed for the determination of the stability constant of the complex; the advantages and disadvantages of the different approaches are also discussed. Inclusion complex formation was also assessed by molecular modelling study. Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by IR and XRD. The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. Kinetic analysis of POM release from lyophilized complex shows that Korsmeyer-Peppas and Weibull model described the best the dissolution kinetics. The cytotoxicity of the complex was tested against the LP-1 human myeloma cell line which revealed that supramolecular interactions did not significantly affect the anti-cancer activity of the drug. Overall, our results suggest that the inclusion complexation of POM with SBE-β-CD could be a promising approach for developing more effective POM formulations with increased solubility.