Research on solubility, solvent effect and thermodynamics analysis of Lisinopril dissolution and molecular dynamics simulation

IF 2.2 3区工程技术 Q3 CHEMISTRY, PHYSICAL

Journal of Chemical Thermodynamics Pub Date : 2025-02-27 DOI:10.1016/j.jct.2025.107474

Yang Yu, Yue Wang, Cunbin Du

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引用次数: 0

Abstract

The knowledge of solubility is indispensable in the pharmaceuticals development, crystal forms design, manufacturing and application. The high-quality solubility facilitates the selection of appropriate solvents for the formulation and purification of pharmaceutical products. In this study, the phase equilibrium of Lisinopril was established in ethanol, 1-propanol, 2-propanol, 1-butanol, acetone, acetonitrile, ethyl acetate, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), as well as mixtures of DMSO + ethanol and DMSO +2-propanol. The solubility, solvent effect discussion, molecular dynamics (MD) simulations, molecular interaction analysis, model correlation and thermodynamics evaluation were all conducted. The outcomes of Lisinopril solubility in molarity show a direct correlation with temperature, and the rank was as listed: DMSO (1.013 × 10⁻³, 318.15 K) > ethanol (3.887 × 10⁻⁴, 318.15 K) > 1-propanol (3.277 × 10⁻⁴, 318.15 K) > NMP (2.292 × 10⁻⁴, 318.15 K) > 1-butanol (1.642 × 10⁻⁴, 318.15 K) > DMF (1.217 × 10⁻⁴, 318.15 K) > 2-propanol (8.504 × 10⁻⁵, 318.15 K) > acetone (5.212 × 10⁻⁵, 318.15 K) > acetonitrile (3.201 × 10⁻⁵, 318.15 K) > ethyl acetate (1.851 × 10⁻⁵, 318.15 K). The solubility of Lisinopril in DMSO +2-propanol increased with the increasing content of DMSO, however, co-solvency phenomenon exhibited at w = 0.80 in mixture of DMSO + ethanol, and the maximum solubility is 1.271 × 10⁻³ (3.21-fold increase). The molecular interaction was discussed by preferential solvation in depth. Solvent effect was evaluated by KAT-LSER model which concluded that solute-solvent interactions significantly affect solubility more than solvent-solvent interactions. The contributions of solute-solvent interactions and solvent-solvent interactions 71.01 % and 28.99 %. Furthermore, MD simulation at the molecular level showed that hydrogen bonds can form more readily between molecules and play a crucial role in enhancing dissolution of Lisinopril. Additionally, the Apelblat, Wilson, Jouyban-Acree and Apelblat-Jouyban-Acree models were applied to correlate the Lisinopril solubility data. The greatest values of relative average deviation (RAD) and root-mean-square deviation (RMSD) values were 1.75 % and 1.68 × 10⁻⁵, respectively. Finally, the values of thermodynamic properties were all positive which indicated that the dissolution of Lisinopril was an endothermic and entropy increment process.

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来源期刊

Journal of Chemical Thermodynamics 工程技术-热力学

CiteScore

5.60

自引率

15.40%

发文量

199

审稿时长

79 days

期刊介绍： The Journal of Chemical Thermodynamics exists primarily for dissemination of significant new knowledge in experimental equilibrium thermodynamics and transport properties of chemical systems. The defining attributes of The Journal are the quality and relevance of the papers published. The Journal publishes work relating to gases, liquids, solids, polymers, mixtures, solutions and interfaces. Studies on systems with variability, such as biological or bio-based materials, gas hydrates, among others, will also be considered provided these are well characterized and reproducible where possible. Experimental methods should be described in sufficient detail to allow critical assessment of the accuracy claimed. Authors are encouraged to provide physical or chemical interpretations of the results. Articles can contain modelling sections providing representations of data or molecular insights into the properties or transformations studied. Theoretical papers on chemical thermodynamics using molecular theory or modelling are also considered. The Journal welcomes review articles in the field of chemical thermodynamics but prospective authors should first consult one of the Editors concerning the suitability of the proposed review. Contributions of a routine nature or reporting on uncharacterised materials are not accepted.