Improving properties of baricitinib due to interaction with Pluronic micelles

Baricitinib is a new generation medicinal compound that has been recommended for the treatment of rheumatoid arthritis in 2017 as well as alopecia areata and COVID-19 in 2022. The use of baricitinib is complicated by its poor aqueous solubility and unwanted side effects. Therefore, the aim of this work is an improvement of the baricitinib solubility using Pluronic micelles. The effect of the micelles on the solubility and membrane permeability of baricitinib is revealed using the isothermal saturation method and the Franz diffusion cell, respectively. It was observed that degree of baricitinib solubilization depends on the Pluronics structure and pH. The regularities of the interaction of the drug with the micelles were established by means of light scattering and 1D and DOSY 1H NMR. It was demonstrated that the ionization state of baricitinib, depending on pH, affects the drug ability to be included in the micelles. The most effective solubilizer of baricitinib among the Pluronics under study was proposed. The data obtained may be useful for the development of water-soluble formulations of baricitinib.