Engineering Proceedings (Nov 2023)
A New Approach to the Preparation of Inclusion Complexes with Cyclodextrins: Studying Their Stability Using Molecular Dynamics Methods
Abstract
One of the key characteristics of pharmaceutical substances is their solubility in pharmaceutically relevant media. This characteristic reflects the quality of the drug and the rate at which the pharmaceutical substance is released from its dosage form. Reduced efficacy and difficulties in the medical use of pharmaceutical substances are often associated with their low solubility in aqueous solutions. It is worth noting that about 40% of pharmaceuticals are practically insoluble, given that 85% are intended for oral administration, which is the simplest and most convenient form. The encapsulation of drug substances can solve this problem. The modern pharmaceutical industry uses molecular containers such as cyclodextrins for this purpose. The incorporation of the target component occurs on a host–guest basis and is driven by weak intermolecular interactions, the nature of which is not yet fully understood. Encapsulation has been shown to promote stability during storage, improve palatability, enhance pharmacological activity and bioavailability, reduce side effects, and, most importantly, increase the solubility of these substances. Our study presents the synthesis of the nimesulide inclusion complex in β-, γ-cyclodextrin cavity. The experimental results were confirmed using TLC, HPLC, UV- and IR spectroscopy, and X-ray diffraction analysis. The theoretical justification of the stability of the β-cyclodextrin/nimesulide complex was performed via one of the most innovative methods, the molecular dynamics method, using NAMD V2.14 and Gaussian 09W software with a simulation step of 2 femtoseconds and a duration of 5 nanoseconds. A modified CHARMM36 force field was used as the MD force field. The ability to enhance drug solubility and maintain drug stability is a promising area in the field of pharmaceutical chemistry.
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