Mikhail A. Mikhailenko

The effect of carboxylic acids on glycine polymorphism, salt and co-crystal formation. A comparison of different crystallisation techniques

The effect of carboxylic acids on glycine polymorphism, salt and co-crystal formation was compared for slow evaporation of solutions at ambient conditions, spray drying, “fast” and “slow” anti-solvent crystallisation and dry co-grinding. Different phases were found to crystallise from the same starting components, depending on the preparative technique. Small amounts of most carboxylic acids (glutaric acid being the only exception) promoted crystallisation of the γ-polymorph in solution and as a result of co-grinding. When added in equimolar quantities, the same carboxylic acids formed salts with glycine (addition of glutaric acid resulted in co-crystal formation) on slow evaporation of solutions and on co-grinding. Neither succinic nor L-malic acids produced glycine salts, but instead promoted formation of γ-glycine when present in any amount. Anti-solvent crystallisation and spray drying of solutions containing small or large amounts of carboxylic acids produced a variety of glycine polymorphs as both pure phases and their mixtures, whereas only oxalic acid yielded salts. The ability to synthesise glycinium semi-oxalate form II by spray drying was demonstrated.

Mechanochemical Synthesis of Nanocomposites of Drugs with Inorganic Oxides

The nanocomposites of piroxicam and indomethacin with fine porous inorganic oxides, alumina, silica, and magnesia, were obtained by high energy ball milling. Except for the piroxicam–alumina system, the composites revealed higher dissolution rate and solubility of the drugs as compared to the initial ones. The changes in the IR spectra suggested the interaction of the components during ball milling. It was assumed that the formation of new bonds at the contacts of particles in the composite resulted in stabilization of drugs in a metastable state inhibiting their transition into the initial crystalline form.

Supramolecular architecture of betulin diacetate complexes with arabinogalactan from Larix sibirica.

Supramolecular ensembles of arabinogalactan (AG) and its complexes with betulin diacetate (BDA) were studied in water and dimethyl sulfoxide (DMSO) using ablation, induced by submillimeter radiation from the free electron laser. Solutions of 1wt% AG resulted in formation of aerosol particles with a maximum size of 60-70nm. In contrast, with DMSO as the solvent, the majority of particles were significantly smaller. Nevertheless, the addition of water shifted the particle size distribution to a larger size, suggesting the cross-linking of AG chains due to hydrogen bonding through water molecules. The ensembles of molecules were larger in solutions of the AG-BDA complex as compared to pure AG aqueous solution, and the distribution was narrow. The role of side chain interactions in the formation of AG-BDA complexes in aqueous solutions was confirmed by NMR.

New composites of betulin esters with arabinogalactan as highly potent anti-cancer agents.

Abstract Betulin and its esters are the natural compounds with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of these compounds has limited their applications. We prepared new composites of betulin esters using two methods, namely ball-milling of the mixtures of betulin esters with arabinogalactan and preparation of thin films of these mixtures by evaporating the aqueous solutions. These composites revealed higher water solubility as compared with the initial substances without losing the structural integrity and functionality. As a result, the new composites have shown much higher inhibitory effects against different cancer cell lines such as Ehrlich ascites carcinoma cells and lung carcinoma cells (A549) in comparison with the initial substances. The cell viability studies based on Annexin V and Propidium iodide probes have confirmed the high proapoptotic effect of betulin ester derivatives against cancer cells. Graphical abstract

Initial steps of dissolution of monoclinic and rhombic crystals of paracetamol

The initial steps of dissolution of Paracetamol (monoclinic and rhombic modifications) in a series of solvents (10% solutions of acetic anhydride, pyridine, 1,4-dioxane, morpholine, and N-methylmorpholine in CCl4) were studied. The etching patterns on planes parallel and perpendicular to Paracetamol molecular layers were compared.