Improved oral bioavailability of anticancer drug tamoxifen through complexation with water soluble cyclodextrins: in vitro and in vivo evaluation

Erdoğar N., NEMUTLU E., İSKİT A. B., KARA Ş. A., Teksin Z. Ş., BİLENSOY E.

JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY, vol.96, no.1-2, pp.81-91, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 96 Issue: 1-2
  • Publication Date: 2020
  • Doi Number: 10.1007/s10847-019-00952-4
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
  • Page Numbers: pp.81-91
  • Keywords: Oral bioavailability, Tamoxifen, Cyclodextrin, Complexation, Pharmacokinetics, CITRATE, FORMULATION, SOLUBILITY, METHYL, DESIGN, BIOEQUIVALENCE, ENHANCEMENT, DISSOLUTION, STRATEGIES, EFFICACY
  • Hacettepe University Affiliated: Yes


Tamoxifen (TMX), a class II antiestrogen drug consistent with the biopharmaceutical classification system, shows low plasma levels leading to therapeutic failure as a result of poor aqueous solubility. Complexation with multifunctional excipients cyclodextrins (CDs) is an effective technique to increase the bioavailability of low water-soluble drugs in oral dosage forms. In this study, solid complexes were obtained with three cyclodextrins (methyl-beta-cyclodextrin (M-beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sulfobutyl ether beta-cyclodextrin (SBE7-beta-CD)) using co-lyophilization or kneading methods. Physicochemical characterization of solid complexes were performed by differential scanning calorimetry and Fourier transform infrared spectroscopy. The obtained results demonstrated that co-lyophilization method comprises stable inclusion complexes between TMX and cyclodextrins. Dissolution study exhibited that aqueous solubility of TMX was significantly enhanced by complexation with methyl-beta-CD. Consequently, tablet formulation using co-lyophilized complex of TMX and M-beta-CD (1:1) with drug dose equivalent to 10 mg was prepared by direct compression method. 99% drug was released from the formulation at the end of 30 min. From the comparative results of dissolution study, it was found that the prepared formulation showed better release properties than commercial TMX tablets. Animal studies were performed with tablet formulation of TMX:M-beta-CD and commercial tablet formulation administered to Sprague-Dawley rats by oral gavage. Peak concentration (Cmax) of tablet formulation containing TMX/M-beta-CD inclusion complex in mice was efficaciously enhanced twofold over commercial tablet. In conclusion, complexation of TMX with M-beta-CD gives a more effective tablet formulation with improved dissolution and enhanced oral bioavailability which can be promising for the formulation of tamoxifen.