Formation mechanism of a new carbamazepine/malonic acid cocrystal polymorph
- 作者：Waree Limwikrant ; Aiko Nagai ; Yumi Hagiwara ; Kenjirou Higashi ; Keiji Yamamoto ; Kunikazu Moribe ; moribe@p.chiba-u.ac.jp
- 关键词：CBZ ; carbamazepine ; API ; active pharmaceutical ingredient ; MA ; malonic acid ; PM ; physical mixture ; GM ; ground mixture ; PXRD ; powder X-ray diffraction ; FT-IR ; Fourier transform infrared ; DSC ; differential scanning calorimetry ; Cryo ; cryogenic ; RH ; relative
- 刊名：International Journal of Pharmaceutics
- 出版年：2012
- 期刊代码：24_03785173
- 类别：pha
- 出版时间：15 July, 2012
- 卷：431
- 期：1-2
- 页码：237-240
- 文件大小：762 K
摘要
A new 2/1 carbamazepine (CBZ)/malonic acid (MA) cocrystal polymorph form C was formed using a vibrational rod mill, whereas the known cocrystal polymorph form A was prepared using a ball mill. IR measurements showed that the interaction between CBZ and MA in cocrystal form C was formed by amide-carboxylic acid heterosynthons, similar to that in cocrystal form A. However, NMR results showed that the molecular states of CBZ at the dibenzazepine ring appeared to be different, which could be due to variation in either the conjugation of the aromatic rings or the 蟺-蟺 interaction of CBZ. Factors affecting the formation of cocrystal polymorphs, such as heat and force, were investigated to clarify the formation mechanism.