The article “Exploring the solid form landscape of antifungal drug Isavuconazole: crystal structure analysis, phase transformation behavior and dissolution performance” (https://doi.org/10.1039/D1CE01353J) authored by a group of scientists from Laboratory 4-1 headed by Doctor of Chemical Sciences, Professor German L. Perlovich and researchers from Kurnakov Institute of General and Inorganic Chemistry has been included in the HOT Articles 2021 collection of the CrystEngComm journal.
The work is the first study, in which four novel pharmaceutically acceptable solid forms of izavuconazole, a promising latest-generation antifungal compound, have been obtained and investigated. In comparison with its analogues, izavuconazole has a wider spectrum of action and causes less noticeable side effects but its aqueous solubility does not exceed 3 mg/l, which means its delivery inside the human body requires special mechanisms.
The study reported in CrystEngComm is the first successful attempt to solve the crystal structures of izavuconazole, its crystallohydrate and two salts with phosphoric and para-toluene sulphonic acids and to determine their pharmaceutically relevant properties. Based on the experimental data and crystal lattice energy calculations it is shown that the hydrate is the most stable izavuconazole phase under regular conditions. Experiments in aqueous buffer solutions have shown that, when dissolved, izavuconazole and its hydrate preserve their structure, whereas the other species transform into the crystallohydrate form in the presence of water in two hours. In the first few minutes after the dissolution, fast release of izavuconazole molecules from salt and amorphous forms is observed, which increases the active substance concentration by up to 3.5 times. Tabletting of the salt forms slows down the phase transformation into the hydrate and leads to longer supersaturation of the solution.
