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A new approach to the synthesis of inclusion complexes with cyclodextrins and the study of their stability using molecular dynamics methods
* 1 , * 2 , * 2 , 3 , 2
1  Federal State Budgetary Educational Institution of Higher Education "Burdenko Voronezh State Medical University. N.N. Burdenko Voronezh State Medical University, Ministry of Healthcare of the Russian Federation Department of Oncology
2  Kursk State University
3  National Research Nuclear University MEPhI
Academic Editor: Elisabeta Szerb


One of the key characteristics of pharmaceutical substances is their solubility in pharmaceutically significant mediums. This characteristic reflects the quality of the medication and the rate at which the pharmaceutical substance is released from its dosage form. Decrease in efficiency and difficulty in medical application of pharmaceutical substances is often associated with their low solubility in aqueous solutions. It's worth noting that around 40% of medicinal products are practically insoluble, given that 85% are intended for oral administration, which is the simplest and most convenient form. The encapsulation of medicinal substances can address this issue. In the modern pharmaceutical industry, molecular containers such as cyclodextrinsare used for this purpose. Inclusion of the target component occurs in a "host-guest" manner and is dictated by weak intermolecular interactions, the nature of which is not yet fully understood. It has been proven that encapsulation contributes to stability during storage, improved taste qualities, enhanced pharmacological activity and bioavailability, reduced side effects, and most importantly, increased solubility of these substances. Our study presents the synthesis of an inclusion complex of nimesulide into the cavity of β-, γ-cyclodextrin. The results of the experiment were confirmed using TLC, HPLC, UV- and IR-spectroscopy, as well as X-ray structural analysis. The theoretical substantiation of the stability of the β-cyclodextrin/nimesulide complex was carried out by one of the most innovative methods, the molecular dynamics method, using the NAMD software at a simulation step of 2 femtoseconds and a duration of 10 nanosecondsThe modified CHARMM36 force field was used as the MD force field. The ability to enhance the solubility of medicinal substances and maintain their stability is a promising direction in the field of pharmaceutical chemistry.

Keywords: bioavailability; inclusion complex; molecular dynamics; cyclodextrins; stability and resilience of organic compounds