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Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs
Published on: July 27, 2022
Alternative oral exemestane formulation: improved dissolution and permeation.
Burçin Yavuz1, Erem Bilensoy, Imran Vural
1Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Ankara, Turkey. burcin@hacettepe.edu.tr
International Journal of Pharmaceutics
|August 4, 2010
Summary
Exemestane (EXE) bioavailability was improved using cyclodextrin complexation. This enhanced solubility and permeability, leading to more effective oral antiestrogen drug formulations.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Medicinal Chemistry
Background:
- Exemestane (EXE) is an irreversible aromatase inactivator for advanced postmenopausal breast cancer.
- EXE exhibits low oral bioavailability (approx. 5%) due to poor water solubility and extensive first-pass metabolism.
- Cyclodextrin (CD) complexation is a known strategy to enhance the solubility and bioavailability of poorly soluble drugs.
Purpose of the Study:
- To design and develop cyclodextrin complexes of exemestane (EXE) in powder and tablet forms.
- To improve the aqueous solubility and in vitro permeability of EXE.
- To evaluate the potential enhancement of oral bioavailability through cyclodextrin complexation.
Main Methods:
- Inclusion complexes of EXE were prepared with methyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, and hydroxypropyl-gamma-cyclodextrin using kneading and colyophilization methods.
- Complexes were characterized using spectroscopic (1H NMR, FT-IR) and analytical (SEM, X-ray, DSC) techniques.
- Dissolution profiles and Caco-2 cell permeability were assessed for EXE:CD complexes and tablet formulations.
Main Results:
- Both EXE:CD inclusion complexes and tablet formulations demonstrated significantly improved dissolution profiles.
- Cyclodextrin complexation resulted in a 3-fold increase in the apparent permeability constant of EXE in Caco-2 cell studies.
- Randomly methylated-beta-cyclodextrin showed particular efficacy in complex formation.
Conclusions:
- Complexation of EXE with cyclodextrin derivatives effectively enhances its aqueous solubility and dissolution.
- The developed cyclodextrin formulations exhibit improved drug permeation, suggesting enhanced oral bioavailability.
- Randomly methylated-beta-cyclodextrin offers a promising approach for developing more efficient exemestane tablet formulations.
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