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Journal of Chemistry
Volume 2017, Article ID 4537632, 9 pages
Research Article

Physicochemical Characterization and Cyclodextrin Complexation of the Anticancer Drug Lapatinib

1Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre U. 9, Budapest 1092, Hungary
2Department of Drugs Industry and Pharmaceutical Management, University of Medicine and Pharmacy, Gh. Marinescu 38, 540139 Târgu Mureș, Romania

Correspondence should be addressed to Arash Mirzahosseini; uh.vinu-siewlemmes.amrahp@hsara.iniessohazrim

Received 24 November 2016; Accepted 9 February 2017; Published 1 March 2017

Academic Editor: Jaime Villaverde

Copyright © 2017 Gergő Tóth et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Lapatinib (LAP), the tyrosine kinase inhibitor drug with moderate bioavailability, was characterized in terms of physicochemical properties: acid-base characteristics, lipophilicity, and solubility. The highly lipophilic nature of the drug and its extremely low water solubility ( nM) limit the development of a parenteral formulation. In order to enhance solubility and bioavailability, inclusion complex formation with cyclodextrins (CDs) is a promising method of choice. Therefore, LAP-CD interactions were also studied by a multianalytical approach. The stability constants of LAP with native cyclodextrins, determined by UV spectroscopy, identified the seven-membered β-CD as the most suitable host. Continuous variation method (Job’s plot) by 1H NMR showed a 1 : 1 stoichiometry for the complexes. The geometry of the complex was elucidated by 2D ROESY NMR measurements and molecular modeling, indicating that the partial molecular encapsulation includes the fluorophenyl ring of LAP. Phase-solubility studies with four CDs, β-CD, (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), randomly methylated-β- (RAMEB-) cyclodextrin, and sulfobutylether-β-cyclodextrin (SBE-β-CD), show an type diagram and highly increased solubility via CD complexation. The results are especially promising with SBE-β-CD, exerting more than 600-fold gain in solubility. The equilibrium and structural information presented herein can offer the molecular basis for an improved drug formulation with enhanced bioavailability.