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抗心血管药物插层层状双氢氧化物纳米杂化物的体外释放动力学和稳定性。

In-vitro release kinetics and stability of anticardiovascular drugs-intercalated layered double hydroxide nanohybrids.

机构信息

Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology, Bombay, Mumbai-400076, India.

出版信息

J Phys Chem B. 2009 Nov 12;113(45):15090-100. doi: 10.1021/jp905440e.

Abstract

We report the intercalation and characterization of pravastatin and fluvastatin drugs in Mg(II)/Al(III) layered double hydroxides (LDHs) to form novel nanohybrid hydroxides through the coprecipitation technique. powder X-ray diffraction, Fourier transform infrared spectroscopy, and thermal analysis techniques reveal that the drugs are accommodated within the brucite layers. Structural characterization, computed results, and atomic force microscopy image analysis demonstrate that the fluvastatin anions are attached with the brucite as a monolayer, whereas the pravastatin anions form a multilayer. The shift in the stretching frequency of carboxylate anion of statin drugs provides evidence that the drugs are electrostatically bonded to LDHs. X-ray diffraction and thermal analysis studies performed after keeping the nanohybrid particles at 75 +/- 10% relative humidity atmosphere, indicate their physical stability due to proper confinement of drugs within the layers. In-vitro release study of developed nanohybrid particles suggests that the significant reduction in release rate of fluvastatin anions from fluvastatin intercalated LDHs is due to its hydrophobic nature and it can be further controlled by varying the concentration in physiological medium. After release, the data were fitted to the dissolution-diffusion kinetic model. The mechanism of drugs diffusion in hydrophobic nanohybrid is probably due to heterogeneous diffusion via anion exchange, while in a hydrophilic nanohybrid, it is due to intraparticle diffusion via anion exchange with the anions in the physiological medium.

摘要

我们报告了普伐他汀和氟伐他汀药物在 Mg(II)/Al(III)层状双氢氧化物 (LDHs) 中的插层和表征,通过共沉淀技术形成了新型纳米杂化氢氧化物。粉末 X 射线衍射、傅里叶变换红外光谱和热分析技术表明,药物被容纳在水镁石层之间。结构表征、计算结果和原子力显微镜图像分析表明,氟伐他汀阴离子与水镁石作为单层结合,而普伐他汀阴离子形成多层。他汀类药物羧酸根阴离子伸缩频率的位移提供了药物与 LDHs 静电结合的证据。将纳米杂化颗粒保持在 75 +/- 10%相对湿度气氛下进行的 X 射线衍射和热分析研究表明,由于药物在层内的适当限制,它们具有物理稳定性。开发的纳米杂化颗粒的体外释放研究表明,氟伐他汀阴离子从氟伐他汀插层 LDHs 中的释放率显著降低是由于其疏水性,并且可以通过改变生理介质中的浓度进一步控制。释放后,数据拟合溶解-扩散动力学模型。药物在疏水性纳米杂化中的扩散机制可能是由于通过阴离子交换的非均相扩散,而在亲水性纳米杂化中,由于通过阴离子交换与生理介质中的阴离子进行的颗粒内扩散。

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