Molecular dynamics, physical stability and solubility advantage from amorphous indapamide drug.
Molecular dynamics, physical stability and solubility advantage from amorphous indapamide drug.
复制标题
无定形吲达帕胺药物的分子动力学、物理稳定性和溶解度优势。
DOI：
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发表时间：
2013
影响因子：
4.9
通讯作者：
Jarosław Markowski
中科院分区：
文献类型：
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作者：
Z. Wojnarowska;K. Grzybowska;Lukasz Hawelek;M. Dulski;Roman Wrzalik;I. Gruszka;M. Paluch;K. Pieńkowska;Wiesław Sawicki;P. Bujak;K. Paluch;L. Tajber;Jarosław Markowski
本研究首次对非晶态吲哚帕胺药物（IND）的理化性质进行了研究，IND是一种常用的用于治疗高血压的利尿剂。采用x射线粉末衍射（XRD）、质谱、核磁共振（NMR）、红外光谱（FT-IR）、差示扫描量热法（DSC）和宽带介电光谱（BDS）分析了玻璃化、冷磨和球磨IND样品的固态性质。这些分析技术使我们能够(i)确认获得的非晶样品的纯度，（ii）描述液态和玻璃态IND的分子迁移率，（iii）确定描述液-玻璃转变的参数，即Tg和动态脆性，（iv）测试非晶IND在各种温度条件下的化学稳定性，最后(v)确认非晶样品的长期物理稳定性。这些研究补充了密度泛函理论（DFT）计算和无定形IND在0.1 M HCl，磷酸盐缓冲液（pH=6.8）和水（25和37°C）中的表观溶解度研究。
This study for the first time investigates physicochemical properties of amorphous indapamide drug (IND), which is a known diuretic agent commonly used in the treatment of hypertension. The solid-state properties of the vitrified, cryomilled and ball-milled IND samples were analyzed using X-ray powder diffraction (XRD), mass spectrometry, nuclear magnetic resonance (NMR), infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). These analytical techniques enabled us (i) to confirm the purity of obtained amorphous samples, (ii) to describe the molecular mobility of IND in the liquid and glassy state, (iii) to determine the parameters describing the liquid-glass transition i.e. Tg and dynamic fragility, (iv) to test the chemical stability of amorphous IND in various temperature conditions and finally (v) to confirm the long-term physical stability of the amorphous samples. These studies were supplemented by density functional theory (DFT) calculations and apparent solubility studies of the amorphous IND in 0.1 M HCl, phosphate buffer (pH=6.8), and water (25 and 37 °C).