Preparation, characterization, and in vitro cytogenotoxic evaluation of a novel dimenhydrinate-β-cyclodextrin inclusion complex

Authors

  • Lamija Hindija Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Jasmina Hadžiabdić Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Anja Haverić Laboratory for Cytogenetics and Genotoxicology, Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Ognjenka Rahić Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0003-0183-1124
  • Maida Hadžić Omanović Laboratory for Cytogenetics and Genotoxicology, Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Lejla Čaluk Klačar Laboratory for Cytogenetics and Genotoxicology, Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0001-9953-2645
  • Irma Durmišević Laboratory for Cytogenetics and Genotoxicology, Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Amina Tucak Smajić Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0002-5149-8860
  • Merima Šahinović Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Edina Vranić Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

DOI:

https://doi.org/10.17305/bb.2024.10507

Keywords:

Dimenhydrinate, β-cyclodextrin, phase solubility, FTIR, DSC, MTT assay, alkaline comet assay, CBMN-cyt

Abstract

Dimenhydrinate (DMH), used to alleviate motion sickness symptoms such as nausea, vomiting, dizziness, and vertigo, encounters limitations in oral pharmaceutical formulations due to its poor water solubility and bitter taste. Our research hypothesized that inclusion complexation with β-cyclodextrin (β-CD) might address these drawbacks while ensuring that the newly formed complexes exhibit no cytotoxic or genotoxic effects on peripheral blood mononuclear cells (PBMCs). Inclusion complexes were prepared using the kneading method and the solvent evaporation method. The phase solubility analysis, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC) were conducted to evaluate the complexation efficacy and stability constant of the new binary systems. The results demonstrated that both methods provided complete and efficient complexation. Cytogenotoxic analysis, including the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline comet assay, and cytokinesis-block micronucleus cytome (CBMN-cyt) assay, was conducted to assess the cytogenotoxic potential of DMH-β-CD inclusion complexes, a topic previously unexamined. No cytotoxic or genotoxic effects were observed within the concentration range of 36.36 to 109.09 ng/mL. Cell viability of treated PBMCs exceeded 85% for all tested concentrations. No significant increases in DNA strand breaks were observed at any dose, and tail intensity of all complexes remained lower or up to 2.2% higher than the negative control. Parameters indicating genotoxic effects, as well as cytotoxic and cytostatic potential in the CBMN-cyt assay, did not significantly differ from untreated controls. These results suggest that inclusion complexation with β-CD might be a safe and promising solution to overcome the limitations of poor solubility and unpleasant taste of DMH, potentially providing opportunities for new and improved oral pharmaceutical dosage forms.

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Preparation, characterization, and in vitro cytogenotoxic evaluation of a novel dimenhydrinate-β-cyclodextrin inclusion complex

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Published

17-10-2024

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Research article

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How to Cite

1.
Preparation, characterization, and in vitro cytogenotoxic evaluation of a novel dimenhydrinate-β-cyclodextrin inclusion complex. Biomol Biomed [Internet]. 2024 Oct. 17 [cited 2024 Dec. 11];24(6):1637–1650. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/10507