Mirza Sabiruddin, Miroshnyk Inna, Rantanen Jukka, Aaltonen Jaakko, Harjula Pasi, Kiljunen Eero, Heinämäki Jyrki, Yliruusi Jouko
Division of Pharmaceutical Technology, Faculty of Pharmacy, P.O. Box 56 University of Helsinki, FI-00014 Helsinki, Finland.
J Pharm Sci. 2007 Sep;96(9):2399-408. doi: 10.1002/jps.20894.
Baclofen, a widely used antispastic agent, has been found to exist in two crystalline forms, the anhydrate and monohydrate. The aim of this study was (1) to identify and characterize these two solid phases of baclofen, and (2) to examine the processing-induced phase transformations associated with wet granulation of baclofen. Using multiple techniques (powder X-ray diffraction, thermal analysis, vibrational spectroscopy and water vapor sorption analysis), a structural relationship has been established between the anhydrate and monohydrate of baclofen. Thermal and variable-temperature powder X-ray diffraction data indicate that the monohydrate, which presumably belongs to the channel hydrate class, dehydrates at 60 degrees C with the formation of the anhydrate. Furthermore, the anhydrate to monohydrate transformation followed by optical microscopy was found to occur via a solvent-mediated route. During wet massing experiments, the critical moisture value for the hydrate formation under the conditions of the present study was identified using qualitative powder X-ray diffraction and Raman spectroscopy. Finally, the interconversion pathway between the two crystalline forms of baclofen was presented. The knowledge of this pathway provides better understanding and control of the solid state of baclofen during processing and storage.
巴氯芬是一种广泛使用的抗痉挛药物，已发现它有两种晶型，即无水物和一水合物。本研究的目的是：（1）鉴定和表征巴氯芬的这两种固相；（2）研究与巴氯芬湿法制粒相关的加工诱导相变。通过多种技术（粉末X射线衍射、热分析、振动光谱和水蒸气吸附分析），已建立了巴氯芬无水物和一水合物之间的结构关系。热分析和变温粉末X射线衍射数据表明，一水合物可能属于通道水合物类别，在60℃脱水形成无水物。此外，通过光学显微镜观察发现，无水物向一水合物的转变是通过溶剂介导的途径发生的。在湿法制粒实验中，利用定性粉末X射线衍射和拉曼光谱确定了本研究条件下形成水合物的临界水分值。最后，给出了巴氯芬两种晶型之间的相互转化途径。了解这一途径有助于更好地理解和控制巴氯芬在加工和储存过程中的固态。
