Experimental and DFT Calculation Probing the Interaction of Simvastatin-β-Cyclodextrin-Ammonium Acetate Ternary Complex

IF 1.3 4区化学 Q4 CHEMISTRY, PHYSICAL

Journal of Solution Chemistry Pub Date : 2025-07-10 DOI:10.1007/s10953-025-01475-y

Hanzhu Kong, Xianhong Wen, Ming Guo

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Abstract

Simvastatin(Sim) is widely used for the prevention of cardiovascular disease and cancer treatment, but its solubility and bioavailability are poor. Therefore, the selection of β-cyclodextrin and ammonium acetate was explored to prepare ternary Sim inclusion complexes by freeze-drying method, the formation of ternary complex was confirmed by Electrospray ionization mass spectrometry (ESI-MS), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Scanning electron microscope (SEM), and X-ray diffraction (XRD) method. Compared to its solubility in pure water, the solubility of Sim in ternary complexes has increased by 46 times. The stable structure of complex was explored through 1H Nuclear magnetic resonance spectroscopy (NMR) and Density functional theory (DFT) calculation, Natural Bond Orbital (NBO) analysis revealed the interaction mechanism, where charge transfer and hydrogen bonding networks in the complex led to the locking of the Sim lactone ring within the narrower ring of β-CD, the NH₄Ac component leads to more hydrogen bond formation and enhances stability of drug. The proposed approach is a innovative systems for improving the solubility and stability of Simvastatin.

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辛伐他汀-β-环糊精-乙酸铵三元配合物相互作用的实验与DFT计算

辛伐他汀（Sim）广泛用于心血管疾病的预防和癌症的治疗，但其溶解度和生物利用度较差。因此，选择β-环糊精和乙酸铵，采用冷冻干燥法制备三元Sim包合物，并通过电喷雾电离质谱（ESI-MS）、傅里叶变换红外光谱（FT-IR）、差示扫描量热（DSC）、扫描电镜（SEM）、x射线衍射（XRD）等方法证实三元配合物的形成。与在纯水中的溶解度相比，Sim在三元配合物中的溶解度提高了46倍。通过1H核磁共振波谱（NMR）和密度泛函理论（DFT）计算探索配合物的稳定结构，自然键轨道（NBO）分析揭示了配合物的相互作用机理，配合物中的电荷转移和氢键网络导致Sim内酯环锁定在β-CD的较窄环内，NH4Ac成分导致更多的氢键形成，增强了药物的稳定性。该方法是一种创新的系统，用于提高辛伐他汀的溶解度和稳定性。

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来源期刊

Journal of Solution Chemistry 化学-物理化学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3-8 weeks

期刊介绍： Journal of Solution Chemistry offers a forum for research on the physical chemistry of liquid solutions in such fields as physical chemistry, chemical physics, molecular biology, statistical mechanics, biochemistry, and biophysics. The emphasis is on papers in which the solvent plays a dominant rather than incidental role. Featured topics include experimental investigations of the dielectric, spectroscopic, thermodynamic, transport, or relaxation properties of both electrolytes and nonelectrolytes in liquid solutions.