Exploring the Effects of Cramped-Impact-Type Mechanical Action on Active Pharmaceutical Ingredient (Levofloxacin)—Prospects for Pharmaceutical Applications

Abstract

Mechanochemistry is one of the ten great discoveries of green chemistry methods for synthesizing new substances. A drug substance from the fluoroquinolone group was exposed to high-intensity mechanical impacts using a laboratory knife mill for 21 min and constantly monitored by analyzing samples extracted every 3 min with DLS, SLS, LALLS, 2D-LS, optical and digital microscopy, FTIR, and Spirotox methods. A dispersity phenomenon was detected in an area where catastrophic dislocations formed and multiplied via laser methods. The positive correlation between the temperature of deformation and stress was demonstrated, similar to a typical stress–strain curve of a Bochvar–Oding curve and Young’s modulus: the angular coefficient of the straight section to OX was tgα = 10 min−1. Z-Average, ζ-potential, and polydispersity index dependences were represented as discontinuous periodic oscillations analogous to the defect and impurity transitions near the dislocation core. Deformation r from the high-intensity mechanical impact resulted in covalent bonds showing hyper- and hypochromic effects under FTIR spectra, a bathochromic shift of the maximum, and an oscillation emission at 3240 cm−1. A 2D-LS fingerprint diagram obtained via the topological convolution of the light scattering matrix made it possible to distinguish the off-loading samples from the native substance. The investigation of the dissolution kinetics in water via laser diffraction led to conclusions about the limiting diffusion stage and the acceleration of the mechanoactivation of the solid body’s dissolution under both linear and plastic deformation. The acceleration of obsEa of the cell death process in the temperature range from 296 to 302 K indicated a significant (2.5-fold) decrease in the toxicity of the aqueous 9 mM (1:3) sample solution at 21 min compared to that of the native levofloxacin. Adherence to the mechanochemistry laws provides an opportunity for drug repositioning to change their brand status by identifying new physicochemical and biological properties.

Influence of Mechanical Loading on the Process of Tribochemical Action on Physicochemical and Biopharmaceutical Properties of Substances, Using Lacosamide as an Example: From Micronisation to Mechanical Activation

“…The figure shows the dispersity phenomenon (DPh) previously described in [ 40 , 41 , 42 , 43 , 44 ]. In this study, the DPh phenomenon is observed in the increase in diameter (d, μm) and volume fraction (%) of size groups of Lcs particles in the ongoing micronisation process at high-intensity ML applied to the solid.…”

“…Thus, the micronisation of Lcs particles is accompanied by deformation and aggregation of crystals, amorphization and formation of centres with increased activity, which can result in increased reactivity [46]. The figure shows the dispersity phenomenon (DPh) previously described in [40][41][42][43][44]. In this study, the DPh phenomenon is observed in the increase in diameter (d, µm) and volume fraction (%) of size groups of Lcs particles in the ongoing micronisation process at high-intensity ML applied to the solid.…”

In Silico Activity Prediction and Docking Studies of the Binding Mechanisms of Levofloxacin Structure Derivatives to Active Receptor Sites of Bacterial Type IIA Topoisomerases

“…The one of the real (6-decarboxylated) Lvf chemical structure derivatives were obtained by tribochemical method based on the intensive impact and cutting loads on the solid [39]. For this purpose, a Stegler LM-250 milling mechanoactivator with a brush motor (Shenzhen Bestman Instrument CO., Ltd., Shenzhen, China), rotation speed 28,000 rpm, power 13 kW, was used.…”