Andrei V. Shabatin

The use of medicinal substances in nanosized forms (nanoforms, nanoparticles) allows the therapeutic effectiveness of pharmaceutical preparations to be increased due to several factors: (1) the high specific surface area of nanomaterials, and (2) the high concentration of surface-active centers interacting with biological objects. In the case of drug nanoforms, even low concentrations of a bioactive substance can have a significant therapeutic effect on living organisms. These effects allow pharmacists to use lower doses of active components, consequently lowering the toxic side effects of pharmaceutical nanoform preparations. It is known that many drug substances that are currently in development are poorly soluble in water, so they have insufficient bioavailability. Converting them into nanoforms will increase their rate of dissolution, and the increased saturation solubility of drug nanocrystals also makes a significant contribution to their high therapeutic efficiency. Some physical and chemical methods can contribute to the formation of both pure drug nanoparticles and their ligand or of polymer-covered nanoforms, which are characterized by higher stability. This review describes the most commonly used methods for the preparation of nanoforms (nanoparticles) of different medicinal substances, paying close attention to modern supercritical and cryogenic technologies and the advantages and disadvantages of the described methods and techniques; moreover, the improvements in the physico-chemical and biomedical properties of the obtained medicinal nanoforms are also discussed.

Increasing the effectiveness of known, well-tested drugs is a promising low-cost alternative to the search for new drug molecular forms. Powerful approaches to solve this problem are (a) an active drug particle size reduction down to the nanoscale and (b) thermodynamically metastable but kinetically stable crystal modifications of drug acquisition. The combined cryochemical method has been used for size and structural modifications of the antibacterial drug 2,3-quinoxalinedimethanol-1,4-dioxide (dioxidine). The main stage of the proposed technique includes the formation of a molecular vapor of the drug substance, combined with a carrier gas (CO₂) flow, followed by a fast condensation of the drug substance and CO₂ molecules on a cooled-by-liquid nitrogen surface of preparative cryostate. It was established that the molecular chemical structure of the drug substance remained unchanged during cryochemical modification; however, it led to a significant decrease of the drug particles’ size down to nanosizes and changes in the crystal structures of the solid drug nanoforms obtained. Varying carrier gas (CO₂) flow led to changes in their solid phase composition. A higher dissolution rate and changes in antibacterial activity were demonstrated for cryomodified dioxidine samples in comparison to the properties of the initial pharmacopeia dioxidine.