Simulation of the desorption process of desloratadine from alloys with polyethylene glycol-1500 (PEG) using the molecular dynamics method
Abstract
Desloratadine, a medicinal product with proved antihistamine activity, is currently present in three dosage forms on the pharmaceutical market: pills, solutions, and syrups. A significant factor hindering the development of new medicinal products based on desloratadine is its low solubility in water. It is therefore important to analyse the opportunities for creating new dosage forms of desloratadine which can be more soluble in water. Such dosage forms can be based on solid dispersions. Computer modelling is currently a promising technique used in pharmaceutical technologies to develop drug compositions. The purpose of our study was to perform a comparative analysis of the desorption process of desloratadine from alloys with polyethylene glycol-1500 into the dissolution medium based on the results of simulation of molecular dynamics. The desorption of desloratadine from alloys containing PEG was simulated by means of the molecular dynamics method using Gromacs 2023 programme, Amber 99 force field. The parametrisation of the force field for the molecules of the components in the simulated systems and the assembly of PEG polymer chains were performed using the ParmEd programme. Models of desloratadine alloys containing polyethylene glycol–1500 were built to study the desorption of desloratadine. The molecular dynamics was simulated by means of thermostatting and barostatting with a step of 2 fs for 25 ns. As a result of the simulation, we calculated the energy of interaction between desloratadine, the polymer, and the solvent per one molecule of desloratadine, and the number of desloratadine molecules that lost their bonds with PEG. The study of the desorption of desloratadine from alloys with polyethylene glycol–1500 carried out by means of the molecular dynamics method demonstrated that the maximum desorption of desloratadine with polyethylene glycol–1500 is achieved at the ratio of 1:2.
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