School of Pharmacy, University of Camerino, Camerino, Italy.
School of Pharmacy, University of Camerino, Camerino, Italy.
J Pharm Sci. 2017 Oct;106(10):3084-3094. doi: 10.1016/j.xphs.2017.05.037. Epub 2017 Jun 7.
The present work investigated the solid state change of 4 acyclovir polymorphs when ground at room temperature (Method A) and under cryo-grinding in the presence of liquid nitrogen (Method B). Modifications in particle size and shape (evaluated by scanning electron microscopy) and in the water content (evaluated by thermal analysis) were related to transitions at the solid state, as confirmed by X-ray powder diffractometry. Anhydrous Form I was stable under grinding by both Methods A and B. The anhydrous Form II was stable during grinding under Method A, whereas it was progressively converted to the hydrate Form V during grinding under Method B. The hydrate Form V was stable under Method A, whereas it was converted to the anhydrous Form I after 15 min and then to the hydrate Form VI after 45 min of grinding. The hydrate Form VI proved to be stable under grinding by both Methods A and B. Thus, Form I and VI were the only forms that yielded a sizeable decrease in particle size under grinding, with a consequent increase in particle dissolution rate, while maintaining solid state physicochemical stability. Form I treated under Method B grinding gave the best dissolution rate.
本工作研究了 4 种阿昔洛韦多晶型物在室温下研磨（方法 A）和在液氮存在下冷冻研磨（方法 B）时的固态变化。通过扫描电子显微镜评估的粒径和形状的变化（通过热分析评估的含水量变化）与固态转变有关，这通过 X 射线粉末衍射法得到了证实。无水形式 I 在两种方法 A 和 B 的研磨下均稳定。无水形式 II 在方法 A 研磨下稳定，而在方法 B 研磨下逐渐转化为水合物形式 V。水合物形式 V 在方法 A 下稳定，而在研磨 15 分钟后转化为无水形式 I，然后在研磨 45 分钟后转化为水合物形式 VI。水合物形式 VI 在两种方法 A 和 B 的研磨下均稳定。因此，只有形式 I 和 VI 在研磨下会导致粒径显著减小，从而提高粒子溶解速率，同时保持固态物理化学稳定性。用方法 B 研磨处理的形式 I 给出了最佳的溶解速率。
