Solid-state properties and relationship between anhydrate and monohydrate of baclofen.
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.
Mirza
Sabiruddin
S
Division of Pharmaceutical Technology, Faculty of Pharmacy, P.O. Box 56 University of Helsinki, FI-00014 Helsinki, Finland. sabir.mirza@helsinki.fi
Miroshnyk
Inna
I
Rantanen
Jukka
J
Aaltonen
Jaakko
J
Harjula
Pasi
P
Kiljunen
Eero
E
Heinämäki
Jyrki
J
Yliruusi
Jouko
J
D001418:Baclofen / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D018755:GABA Agonists / Q000737:chemistry*; D006813:Humidity; D008855:Microscopy, Electron, Scanning; D011208:Powders; D013055:Spectrophotometry, Infrared; D019265:Spectroscopy, Near-Infrared; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
D018755:GABA Agonists; D011208:Powders; D001418:Baclofen