Process-Induced Phase Transformation of Berberine Chloride Hydrates
Publication in refereed journal



摘要Berberine is a natural quaternary ammonium alkaloid used clinically in the chloride salt form for the treatment of diarrhea in many Asian countries. Although the hydrate formation of berberine chloride (BC1) is well documented, the associated mechanism and implications in pharmaceutical formulation have not been studied in detail. In this study, pure BC1 dihydrate and BC1 tetrahydrate were recrystallized from water and their phase transformation behaviors under defined conditions were investigated. Additionally, pharmacopoeial grade BC1 material consisting predominantly of the dihydrate form was examined for potential phase changes when being subjected to a conventional wet granulation procedure for tablet production. Results from solubility measurements, thermal analysis, variable temperature-powder X-ray diffraction (VT-PXRD), and variable temperature-Fourier transform infrared spectroscopy (VT-FTIR) confirmed the solid-state interconversions between the tetrahydrate and dihydrate at 30-49 degrees C and between the dihydrate and anhydrate at 70-87 degrees C. Consistent with the observed phase changes of the two pure hydrates, wet massing of the pharmacopoeial grade BC1 sample led to a thermodynamics-driven transition to the tetrahydrate form at room temperature while subsequent tray drying at 50 C caused a reversion back to the dihydrate form. The rate and extent of such hydrate conversion depended largely on the water activity of the granulated powder matrix, which in turn was governed by the particular excipients employed. The present findings have important implications in the regulation of the hydrate forms of BC1 in the finished products using specific excipients. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1942-1954, 2010
著者Tong HHY, Chow ASF, Chan HM, Chow AHL, Wan YKY, Williams ID, Shek FLY, Chan CK
期刊名稱Journal of Pharmaceutical Sciences
頁次1942 - 1954
關鍵詞berberine chloride hydrates; drying kinetics; phase transformation; solid-state transition; wet granulation
Web of Science 學科類別Chemistry; Chemistry, Medicinal; CHEMISTRY, MEDICINAL; Chemistry, Multidisciplinary; CHEMISTRY, MULTIDISCIPLINARY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

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