Improving the solubility of vorinostat using cyclodextrin inclusion complexes: The physicochemical characteristics, corneal permeability and ocular pharmacokinetics of the drug after topical application

• DOI: 10.1016/j.ejps.2021.106078
• Publication Date: 2021-11-24T07:18:52Z
• Authors: Jingjing Yang; Yu Ma; Qing Luo; Zhen Liang; Ping Lu; Fei Song; Zhen Zhang; Tianyang Zhou; Junjie Zhang
• Keywords: Vorinostat

Vorinostat (suberoylanilide hydroxamic acid, SAHA), an FDA-approved drug for cutaneous T cell lymphoma, has antiangiogenic and anti-inflammatory activity thus therapeutic potential inflammatory corneal neovascularization (CNV). However, its practical administration is limited due to poor aqueous solubility permeability. This study aimed enhance the permeability of SAHA by promoting inclusion into a complex with hydroxypropyl-β-CD (HPβCD) topical application. In phase-solubility studies, HPβCD sulfobutyl ether-β-CD (SEβCD) was assessed at different temperatures, complexation efficiencies (K) were calculated. The complexes (ICs) prepared characterized differential scanning calorimetry (DSC), infrared spectrometry (IR), electron microscopy (SEM), X-ray diffraction (XRD) after freeze-drying. showed that higher in solutions (297.35 M-1, 115.28 M-1 122.75 M-1) than SEβCD (169.75 91.33 96.49 4 °C, 25 °C 37 °C. selected SAHA-IC preparation, characterization revealed IC formation. existed amorphous state ICs. ex vivo also evaluated found be greater when formulated as solution suspension. Irritation assays rabbit eyes not irritating ocular pharmacokinetics New Zealand White rabbits following (0.2%), 0.2% suspension used control. Compared formulation suspension, increased bioavailability more 3-fold conjunctival 2-fold. Thus, formation effective improving SAHA. provides important alternative approach developing liquid pharmaceutical formulations applications.