Tsumura Co., Ltd.
Faculty of Pharmaceutical Sciences, Toho University.
Chem Pharm Bull (Tokyo). 2021;69(2):185-198. doi: 10.1248/cpb.c20-00719.
In the drug formulation process, compound dissolution rate and wettability may be improved by grinding. However, there is no method to understand the effects of the wettability of the crystal facets of the ground product. Here, acetylsalicylic acid (ASA) was used to evaluate the changes in crystal morphology and dissolution rate by jet milling using powder X-ray diffraction and in silico simulation. Several cleavage facets were observed in cube crystals, and the (0 0 2) facet was observed in plate crystals. Furthermore, the dissolution rate of the ground samples per unit area decreased with the cleavage of the (1 0 0) and (0 0 2) facets. The polar surface energy of the ground sample decreased with increasing grinding pressure. The simulation results showed that the absolute attachment energy of the (1 0 0) and (0 0 2) facets was lower than that of the other crystal facets. Moreover, atoms with low polarity were present on the crystal surface of (0 0 2). The wettability and dissolution rate of the (0 0 2) facet were worse than those of the (1 0 0) facet. It was suggested that the dissolution rate of the ground sample was affected by the wettability of the crystal facet caused by the cleavage. The cleavability and wettability may be understood by simulation.
在药物制剂过程中，通过研磨可以提高化合物的溶解速率和润湿性。然而，目前还没有方法可以了解研磨产品的晶体面的润湿性的影响。在这里，使用乙酰水杨酸（ASA）通过粉末 X 射线衍射和计算机模拟评估喷射磨碎对晶体形态和溶解速率的变化。在立方晶体中观察到几个解理面，在板状晶体中观察到（002）面。此外，单位面积的研磨样品的溶解速率随（100）和（002）面的解理而降低。研磨样品的极性表面能随研磨压力的增加而降低。模拟结果表明，（100）和（002）面的绝对附着能低于其他晶体面。此外，（002）面上存在极性较低的原子。（002）面的润湿性和溶解速率比（100）面差。因此，研磨样品的溶解速率可能受到晶体面解理引起的润湿性的影响。可通过模拟来理解可解理性和润湿性。
