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利用亲水性载体中的固体分散体系统来增加苯并硝唑的溶解度。

The use of solid dispersion systems in hydrophilic carriers to increase benzonidazole solubility.

机构信息

Laboratório de Tecnologia dos Medicamentos, Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Rua Prof Arthur de Sá, s/n, Cidade Universitária, 50740-521 Recife, PE, Brazil.

出版信息

J Pharm Sci. 2011 Jun;100(6):2443-51. doi: 10.1002/jps.22436. Epub 2011 Jan 6.

Abstract

The present study investigates the release mechanism of benznidazole (BNZ) in solid dispersions with polyethylene glycol 6000 (PEG 6000) and polyvinylpirrolydone K-30 (PVP K-30), with a view to observing the increase in solubility of BNZ in water in the presence of these two hydrophilic polymers. The interaction of BNZ with the polymers was evaluated using scanning electron microscopy, Fourier-transformation infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and in vitro dissolution tests, and a theoretical study of molecular modeling was also carried out. The drug-polymer interaction was studied trough molecular modeling, using density functional theory with the B3LYP exchange correlation function. The corrected interaction energies were calculated to be -20.9 kJ/mol with PVP and -6.6 kJ/mol with PEG. The experimental and theoretical results indicate that a powerful interaction occurred between BNZ and the polymers, which was especially strong in the case of PVP, and that this interaction contributed to improvement of BNZ solubility.

摘要

本研究考察了苯并咪唑(BNZ)在聚乙二醇 6000(PEG 6000)和聚乙烯吡咯烷酮 K-30(PVP K-30)固体分散体中的释放机制,以期观察在这两种亲水性聚合物存在的情况下 BNZ 在水中溶解度的增加。使用扫描电子显微镜、傅里叶变换红外光谱、差示扫描量热法、X 射线衍射和体外溶解试验评估了 BNZ 与聚合物的相互作用,并进行了理论研究的分子建模。通过密度泛函理论与 B3LYP 交换相关函数,对药物-聚合物相互作用进行了分子建模研究。计算得到的修正相互作用能分别为-20.9 kJ/mol(与 PVP)和-6.6 kJ/mol(与 PEG)。实验和理论结果表明,BNZ 与聚合物之间发生了强烈的相互作用,特别是与 PVP 之间的相互作用更强,这种相互作用有助于提高 BNZ 的溶解度。

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