Scientists at NSU have found a way to change the direction of mechanochemical transformations involving solid pharmaceutical substances

The results of the study of the features of mechanochemical transformations in the system “pyroxicam – succinic acid” were published in the flagship international journal RSC Mechanochemistry (A. Golomolzin, E. A. Losev and E. Boldyreva. Unlocking the reversibility of the mechanochemical synthesis of a pharmaceutical cocrystal. RSC Mechanochem., 2026, DOI: 10.1039/D6MR00052E; available for download in open accessby the link). The basis of the publication is part of the bachelor’s thesis of a student of the Department of Solid State Physics of the Faculty of Natural Sciences of Novosibirsk State UniversityArtyom Golomolzin, who defended a diploma with distinction in June of this year. The work was carried out with the support of the RSF grant No. 24-13-00140 “Mechanochemical synthesis and mechanochemical recrystallization in a liquid medium: fundamental problems and practical applications” (project leader Doctor of Chemical SciencesFarit Urakaev).

Measured values— the field of physical chemistry that studies processes involving solids occurring under mechanical load. Using this approach has a number of advantages compared to classical solution synthesis: using a small amount of solvents, increased process speed, increased product yield, the possibility of obtaining unusual, metastable phases.

—Pyroxicam is a classic representative of medicinal compounds that can exist both as a neutral molecule and as zwitter-ions (molecular ions that are overall electrically neutral, but contain functional groups with opposite charges within their internal structure). Pyroxicam, like other similar compounds, has low water solubility and high permeability through cellular membranes. The search for solid forms based on pyroxicam with improved dissolution kinetics has so far proceeded by converting the neutral molecule into a zwitter-ion form via amorphization.This improved solubility but negatively affected permeability. An alternative way to increase water solubility—a co-crystallization of pyroxicam with organic acids, in which pyroxicam remains in the form of a neutral molecule—has caused great interest in recent years. Moreover, the results obtained for pyroxicam are relevant and significant for other oxicams—meloxicam, tenoxicam, lornoxicam,— said the professor of the Department of Solid State Physics at NSU, Doctor of Chemical SciencesElena Boldyreva.Â

In a previous work carried out at the Department of Solid State Physics (I.A. Tumanov, A.F. Achkasov, S.A. Myz, E.V. Boldyreva, V.V. Boldyrev, 2014, Doklady Akademii Nauk, 2014, Vol. 457, No. 6, pp. 670–675), using the example of mixed pyroxene crystals, scientists discovered an unusual effect: under shock loading of the co-crystal of pyroxene with succinic acid formed from one component, whereas the grinding load, on the contrary, caused the decomposition of the co-crystal into pyroxene and succinic acid.

—The reasons for this effect remained unclear. In the current published work, we were able to find a way to control this process by using a common commercial mill, combining a change in milling mode with the addition of small amounts of specially selected liquids,— explained the senior lecturer of the Department of Solid State Chemistry at NGU, Candidate of Chemical SciencesEvgeny Losev.

During their research, scientists used various methods capable of more directly confirming or refuting previously proposed hypotheses.

—For the implementation of mechanical action with virtually zero impact load, under other equal experimental conditions, a rotary mill was manufactured using 3D printing, specifically designed for use together with the container of the commercial vibration mill Fritsch Pulverisette 23. We also adapted and applied a rarely used previously method for assessing the intensity of impact in a closed container of the mill, using analysis of the wave shape and sound spectrum emitted by the grinding body moving inside the container of the device., — commentedArtem Golomolzin.

The results of the work done may be useful in the future for controlling and managing mechanochemical processes of obtaining pharmaceutical co-crystals, as well as for a fundamental understanding of the factors influencing such reactions.