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Experimental, molecular docking investigations and bioavailability study on the inclusion complexes of finasteride and cyclodextrins

Authors Mady FM, Farghaly Aly U

Received 18 February 2017

Accepted for publication 20 April 2017

Published 7 June 2017 Volume 2017:11 Pages 1681—1692

DOI https://doi.org/10.2147/DDDT.S135084

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rajendra Narayan Mitra

Peer reviewer comments 3

Editor who approved publication: Dr Tuo Deng

Fatma M Mady,1,2 Usama Farghaly Aly2

1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Taibah University, Medina, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt

Abstract: Finasteride (FIN) is a Class II candidate of the Biopharmaceutics Classification System (BCS). The lipophilic cavity of cyclodextrins (CyDs) enables it to construct a non-covalent inclusion complex with different insoluble drugs. Only β-cyclodextrin (β-CyD) and hydroxypropyl-β-CyD (HP-β-CyD) have been previously examined with FIN. This study aimed to investigate the consistence of FIN with different kinds of β-CyDs, including dimethyl-β-cyclodextrin (DM-β-CyD), carboxymethyl-β-cyclodextrin (CM-β-CyD), HP-β-CyD, sulfobutyl ether-β-cyclodextrin (SBE-β-CyD), and β-CyD, by the coprecipitation method. The resultant inclusion systems were characterized by differential scanning calorimetry, infrared spectroscopy, X-ray diffractometry, and dissolution studies. Moreover, molecular docking for the selected inclusion systems was carried out to explore the suitable arrangements of FIN in the cavity of β-CyD or its derivatives. The results suggested that the DM-β-CyD inclusion system gave the higher complexation efficiency for improvement in solubility of FIN and hence enhancement of its bioavailability. Pharmacokinetic parameters displayed a higher absorption rate and higher area under the curve of the FIN/DM-β-CyD inclusion complex when compared with the drug alone, which indicates an improvement in the absorption and bioavailability of FIN in the DM-β-CyD inclusion system.

Keywords: finasteride, cyclodextrins, molecular docking, pharmacokinetics, bioavailability

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