Hydration Structure and Dynamics of the Favipiravir Antiviral Drug: A Molecular Modelling Approach

Abstract

The hydration structure of the Favipiravir antiviral drug, at infinite dilution in water, was investigated by employing a systematic molecular modelling approach. An effective interaction potential model was employed for Favipiravir, using the intramolecular geometry and charge distribution from quantum chemical calculations performed in the present treatment and adopting well-established Lennard-Jones parameters from the literature. The hydration structure and related dynamics were further investigated by means of classical molecular dynamics simulations. These calculations have revealed the existence of different types of hydrogen bonds between Favipiravir and the surrounding water molecules, with continuous lifetimes in the sub picosecond range and intermittent lifetimes in the range of 0.8-5.4 ps. The self-diffusion coefficient of Favipiravir of 9 2 1 0.58 10 m s − − ⋅ ⋅at 298.15 K was found to be three times lower than the value obtained for water in solution, while comparable to the to the values measured for other common painkillers and antiinflammatory drugs (e.g. paracetamol, aspirin, ketoprofen), antibiotics (e.g. tetracycline, trimethoprim, Penicillin G) and corticosteroids for asthma treatment (beclomethasone, prednisone).It was also revealed that the rotational motions of Favipiravir are more retarded in comparison with water and this is reflected on the calculated reorientational correlation times of specific intramolecular vectors. The results obtained in the present study could be useful in pharmaceutical applications, such as pharmacokinetics and computer-aided docking studies to evaluate the efficiency of this particular antiviral drug.

Novel Formulations of the Antiviral Drug Favipiravir: Improving Permeability and Tabletability

“…Comparatively, the hydrophobic nature was enhanced outside the cavities, which could improve the nonpolar membrane permeability of the FPV-PP salt. 55,64,65 Usually, it is difficult to improve permeability and solubility simultaneously. 56 However, there are some examples that the solubility and permeability of cocrystals or salts were simultaneously improved: for example, the amantadine acetazolamide− piperazine salt 55 and the amantadine hydrochloride−sulfathiazole cocrystal.…”

“…The permeability of an API is affected by many factors, such as polarity, solubility, and size. , Hence, the enhanced permeability of FPV-PP may be explained by its high solubility and special cavity crystal structure which change the polarity of FPV. ,, Due to the high solubility of FPV-PP, the concentration gradients of FPV across the PAMPA membrane are built up quickly and effectively actuate the permeating action. , As described above, the special cavity structure of FPV-PP contains the primary polar functional groups stretching inward. Comparatively, the hydrophobic nature was enhanced outside the cavities, which could improve the nonpolar membrane permeability of the FPV-PP salt. ,, Usually, it is difficult to improve permeability and solubility simultaneously . However, there are some examples that the solubility and permeability of cocrystals or salts were simultaneously improved: for example, the amantadine acetazolamide–piperazine salt and the amantadine hydrochloride–sulfathiazole cocrystal .…”