Modeling of Desloratadine release process from alloys with Polyethylene glycol-6000 by Molecular dynamics method
Abstract
Purpose: Desloratadine is a drug with proven antihistaminic activity, is currently presented on the pharmaceutical market only in dosage forms: tablets, solution and syrup. A significant factor limiting the development of new drugs of desloratadine is its low solubility in water. The actual direction of pharmaceutical technology in this regard is research on creation of dosage forms of desloratadine, aimed at increasing its water solubility. Currently, a promising direction in pharmaceutical technology in the development of drug composition is the use of computer modeling. The use of molecular dynamics
modeling method is very relevant in the development of solid dispersions of drugs. The aim of this study was to carry out molecular dynamics modeling of desloratadine release from alloys with polyethylene glycol-6000 (desloratadine: polymer ratio 1:1, 1:2, 1:5) into the dissolution medium.
Experimental: modeling of desloratadine release from alloys with polyethylene glycol-6000 was carried out by molecular dynamics method (Gromacs 2023 program, Amber 99 force field). The van der Waals interaction energies of desloratadine with polyethylene glycol-6000 and with water were calculated; the fraction of desloratadine molecules that lost the bond with polyethylene glycol-6000. It was found that the average energy of interaction of desloratadine with polyethylene glycol -6000 and with water. Polyethylene glycol-6000 decreases as the content of desloratadine in the alloy decreases. Desloratadine in the alloy, while the interaction energy with water increases.
Conclusions: The studies on the release rate of desloratadine from alloys with polyethylene glycol-6000 by molecular dynamics method showed that the highest release rate of desloratadine was achieved at 1:1 (5.47±1.11 %), 1:2 (5.39±0.51 %) ratios and the lowest at 1:5 (3.03 ± 0.00 %). The obtained results indicate the promising use of solid dispersions “desloratadine – polyethylene glycol-6000” (1:1 ratio)
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