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

Drug Des Devel Ther. 2017 Jun 7:11:1681-1692. doi: 10.2147/DDDT.S135084. eCollection 2017.

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: bioavailability; cyclodextrins; finasteride; molecular docking; pharmacokinetics.

Publication types

  • Comparative Study

MeSH terms

  • 5-alpha Reductase Inhibitors / administration & dosage
  • 5-alpha Reductase Inhibitors / blood
  • 5-alpha Reductase Inhibitors / chemistry
  • 5-alpha Reductase Inhibitors / pharmacokinetics*
  • Administration, Oral
  • Animals
  • Area Under Curve
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Crystallography, X-Ray
  • Drug Compounding
  • Drug Liberation
  • Finasteride / administration & dosage
  • Finasteride / blood
  • Finasteride / chemistry
  • Finasteride / pharmacokinetics*
  • Half-Life
  • Intestinal Absorption
  • Metabolic Clearance Rate
  • Models, Biological
  • Molecular Docking Simulation*
  • Powder Diffraction
  • Rabbits
  • Solubility
  • Spectrophotometry, Infrared
  • beta-Cyclodextrins / chemistry*

Substances

  • 5-alpha Reductase Inhibitors
  • beta-Cyclodextrins
  • Finasteride