Solubilization of vorinostat by cyclodextrins

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Medicinal Chemistry

Background:

• Vorinostat, a histone deacetylase inhibitor, faces challenges in parenteral and oral delivery due to its poor aqueous solubility.
• Hydrophobic nature of vorinostat limits its pharmaceutical applications and bioavailability.

Purpose of the Study:

• To investigate the potential of cyclodextrins (CDs) to improve the aqueous solubility of vorinostat.
• To explore the efficacy of different cyclodextrin derivatives in solubilizing vorinostat.

Main Methods:

• Phase-solubility studies were conducted to quantify vorinostat solubility with various CDs.
• Molecular simulations were used to predict drug-excipient interactions and binding orientations.

Main Results:

• Cyclodextrins substantially increased vorinostat solubility, with efficacy in the order: RM-β-CD > HP-β-CD > α-CD > HP-α-CD > HP-γ-CD > γ-CD.
• Randomly methylated-β-cyclodextrin (RM-β-CD) increased vorinostat solubility by nearly two orders of magnitude.
• Simulation results correlated well with experimental phase-solubility data.

Conclusions:

• Cyclodextrins, especially RM-β-CD and HP-β-CD, are effective in enhancing vorinostat solubility.
• HP-β-CD shows promise for parenteral vorinostat formulations, while RM-β-CD could improve oral absorption.
• Molecular simulation is a valuable tool for selecting suitable cyclodextrins for drug delivery applications.