Erlotinib complexation with randomly methylated beta-cyclodextrin improves drug solubility, intestinal permeability, and therapeutic efficacy in non-small cell lung cancer

Erdogar N., Akkin S., VARAN G., BİLENSOY E.

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, vol.26, pp.797-806, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26
  • Publication Date: 2021
  • Doi Number: 10.1080/10837450.2021.1946695
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Business Source Elite, Business Source Premier, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Page Numbers: pp.797-806
  • Hacettepe University Affiliated: Yes


The purpose of this study was to investigate the impact of anticancer drug erlotinib-randomly methylated-beta-cyclodextrin complex (ERL-RAMEB CD) on drug solubility and dissolution rate. Phase solubility study showed erlotinib displayed maximum solubility in RAMEB CD solution and the stability constant (K-c) was calculated to be 370 +/- 16 M-1. The optimal formulation was obtained with ERL-RAMEB CD in a 1:1 molar ratio using the co-lyophilization technique. Differential scanning calorimetry (DSC) and Scanning electron microscopy (SEM) verified the inclusion of complex formation. In vitro dissolution study confirmed ERL-RAMEB CD as a favorable approach to increase drug dissolution with a 1.5-fold increase than free ERL at 1 h. An improved dissolution with similar to 88.4% drug release at 1 h was observed, in comparison with Erlotinib with similar to 58.7% release in 45 min. The in vitro cytotoxicity results indicated that the ERL-RAMEB CD inclusion complex reduced cell viability than free erlotinib. Caco-2 cell uptake that is indicative of drug intestinal permeability resulted in a 5-fold higher uptake of ERL-RAMEB CD inclusion complex than the ERL solution. Hence, ERL-RAMEB CD complexation displays a strong potential to increase dissolution and permeability of erlotinib leading eventually to enhanced oral bioavailability.