期刊
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 27, 期 6, 页码 523-532出版社
TAYLOR & FRANCIS LTD
DOI: 10.1081/DDC-100105177
关键词
coprecipitation; beta-cyclodextrin; freeze-drying; kneading; spray-drying; tolbutamide
Tolbutamide (TBM) was found to form an inclusion complex with beta -cyclodextrin (beta -CD) in solution and in solid state. Inclusion complex-formation between tolbutamide and A-cyclodextrin in aqueous solution was studied ky phase solubility and spectral shift methods. The apparent stability constant K-s calculated by these techniques, in water, were estimated as 195.7 and 236.5 M-1, respectively. The phase solubility studies revealed a B-S-type diagram with an inclusion complex of 1:2 molar ratio. The solid inclusion complexes of TBM and beta -CD Were prepared at a molar ratio of 1: 2 by kneading, coprecipitation, freeze-drying, and spray-drying methods. In addition, the physical mixture was prepared. Characterization of TBM:beta -CD inclusion was performed using differential scanning calorimetry (DSC), Raman spectroscopy, and X-ray diffractometry and by application of a so-called ether wash method. All the inclusion systems investigated led to a significant improvement in the dissolution over free TBM, and the dissolution rate of the active material was observed to be independent of the preparation method.
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