Favipiravir-Based Ionic Liquids as Potent Antiviral Drugs for Oral Delivery: Synthesis, Solubility, and Pharmacokinetic Evaluation.
Mol Pharm
; 18(8): 3108-3115, 2021 08 02.
Article
in English
| MEDLINE | ID: covidwho-1305357
ABSTRACT
Coronavirus disease 2019 (COVID-19) has spread across the world, and no specific antiviral drugs have yet been approved to combat this disease. Favipiravir (FAV) is an antiviral drug that is currently in clinical trials for use against COVID-19. However, the delivery of FAV is challenging because of its limited solubility, and its formulation is difficult with common organic solvents and water. To address these issues, four FAV ionic liquids (FAV-ILs) were synthesized as potent antiviral prodrugs and were fully characterized by nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectrometry, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), derivative thermogravimetry (DTG), and differential scanning calorimetry (DSC). The aqueous solubility and in vivo pharmacokinetic properties of the FAV-ILs were also evaluated. The FAV-ILs exhibited improved aqueous solubility by 78 to 125 orders of magnitude when compared with that of free FAV. Upon oral dosing in mice, the absolute bioavailability of the ß-alanine ethyl ester FAV formulation was increased 1.9-fold compared with that of the control FAV formulation. The peak blood concentration, elimination half-life, and mean absorption time of FAV were also increased by 1.5-, 2.0-, and 1.5-fold, respectively, compared with the control. Furthermore, the FAV in the FAV-ILs exhibited significantly different biodistribution compared with the control FAV formulation. Interestingly, drug accumulation in the lungs and liver was improved 1.5-fold and 1.3-fold, respectively, compared with the control FAV formulation. These results indicate that the use of ILs exhibits potential as a simple, scalable strategy to improve the solubility and oral absorption of hydrophobic drugs, such as FAV.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Pyrazines
/
Ionic Liquids
/
Amides
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Mol Pharm
Journal subject:
Molecular Biology
/
Pharmacy
/
Pharmacology
Year:
2021
Document Type:
Article
Affiliation country:
Acs.molpharmaceut.1c00324
Similar
MEDLINE
...
LILACS
LIS