Preparation and impregnation of deep eutectic solvents containing zileuton onto adsorbents to elicit the biopharmaceutical attributes

Abstract

Deep eutectic solvent (DES) is a contemporary and eco-friendly solvent recently exploited to modulate the solubility of drugs. Herein, we developed DESs for an increment of solubility and bioavailability of zileuton (ZLT). ZLT is an anti-inflammatory drug categorized as an inhibitor of the enzyme 5-lipoxygenase commonly prescribed for treating chronic bronchial asthma. However, its therapeutic uses are limited owing to its poor water solubility. Several stable DESs were developed and assessed for viscosity, pH, and solubility. The DES comprising ChCl: EG (1:3) exhibits an excellent ZLT solubility (57.27 ± 0.14 mg/mL). The molecular and electrostatic interaction was assessed through a conductor-like screening model for real solvents (COSMO-RS). Further, 1H NMR analysis, FTIR, and digital microscopy were used to investigate the molecular transition in the chosen DES-ZLT. The DES in a liquid state possesses several drawbacks, such as instability, volatility, and dose precision. Therefore, a wet impregnation approach utilizing inert carriers such as Aerosil-200 and Avicel PH-102 was performed for the solidification of liquid DES. The solidified DES-ZLT was characterized by DSC and PXRD techniques and indicated the existence of ZLT in a highly dissolved state. Furthermore, solid DES-ZLT showed a significant increment in the dissolution studies, resulting in a 2.91 fold rise in oral bioavailability of ZLT. Hence, the presented study proves a well-organized and proficient development of a solid DES system to ameliorate the solubility and stability aspects of ZLT, which could provide the template for promising drugs that lack therapeutic effectiveness owing to solubility issues.