Insights into Pharmaceutical Nanocrystal Dissolution: A Molecular Dynamics Simulation Study on Aspirin
Insights into Pharmaceutical Nanocrystal Dissolution: A Molecular Dynamics Simulation Study on Aspirin
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DOI：
10.1021/mp500148q
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发表时间：
2014-09-01
影响因子：
4.9
通讯作者：
Briesen, Heiko
中科院分区：
文献类型：
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作者：
Greiner, Maximilian;Elts, Ekaterina;Briesen, Heiko
所提出的分子动力学模拟是第一次模拟，以揭示其实验确定的形状的药物晶体的动态溶解。通过将粘性虚拟原子平面引入到水板中来确保在周围介质的恒定欠饱和下的连续溶解。这些原子与溶解的阿司匹林分子有很强的相互作用势，但与水的相互作用被排除在计算之外。因此，在溶液中自由扩散的阿司匹林分子的数量保持在低值，并且监测阿司匹林晶体的连续溶解。进一步深入了解具体的脸溶解绘制。对于（001）面，发现了退边的溶解机制。这些结果与实验结果吻合得很好。虽然（100）平面的溶解机制是粗糙表面上的平台下沉，但在本工作中未观察到完全平坦面的明显溶解。因此，药物在其实验获得的结构中的分子模拟已被证明特别适合于溶解面的研究，其中边缘具有显著的效果。与以前的研究相比，溶解前沿到晶面的传播被报道，并且晶体体积在150 ns的整个模拟时间内是稳定的。
The presented molecular dynamics simulations are the first simulations to reveal dynamic dissolution of a pharmaceutical crystal in its experimentally determined shape. Continuous dissolution at constant undersaturation of the surrounding medium is ensured by introducing a plane of sticky dummy atoms into the water slab. These atoms have a strong interaction potential with dissolved aspirin molecules, but interactions with water are excluded from the calculations. Thus, the number of aspirin molecules diffusing freely in solution is kept at a low value and continuous dissolution of the aspirin crystal is monitored. Further insight into face-specific dissolution is drawn. The dissolution mechanism of receding edges is found for the (001) plane. These findings are in good agreement with experimental results. While the proposed dissolution mechanism for the (100) plane is terrace sinking on a rough surface, no pronounced dissolution of the perfectly flat face is seen in the present work. Molecular simulations of pharmaceuticals in their experimentally obtained structure therefore have shown to be especially suited for the investigation of dissolving faces, where the edges have a pronounced effect. In contrast to previous studies a propagation of the dissolution front into the crystal face is reported, and the crystal bulk is stable over the whole simulation time of 150 ns.