Ann Newman - "Assessment of Defects and Amorphous Structure Produced in Raffinose Pentahydrate upon Dehydration" S.Bates, R.Kelly, P.Schields, I.Ivanesvic, G.Zografi, A.Newman

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      Publication Details (including relevant citation   information):

      J. Pharm. Sci., 2007, 96(5),  1418-1433.


      The progressive conversion of crystalline raffinose pentahydrate   to its amorphous form by dehydration at 60°C, well below its   melting temperature, was monitored by X-ray powder diffraction   over a period of 72 h. The presence of defects within the crystal   structure and any amorphous structure created was determined   computationally by a total diffraction method where both coherent   long-range crystalline order and incoherent short-range disorder   components were modeled as a single system. The data were   analyzed using Rietveld, pair distribution function (PDF), and   Debye total diffraction methods. Throughout the dehydration   process, when crystalline material was observed, the average   long-range crystal structure remained isostructural with the   original pentahydrate material. Although the space group symmetry   remained unchanged by dehydration, the c-axis of the   crystal unit cell exhibited an abrupt discontinuity after   approximately 2 h of drying (loss of one to two water molecules).   Analysis of diffuse X-ray scattering revealed an initial rapid   build up of defects during the first 0.5 h with no evidence of   any amorphous material. From 1-2 h of drying out to 8 h where the   crystalline structure is last observed, the diffuse scattering   has both amorphous and defect contributions. After 24 h of   drying, there was no evidence of any crystalline material   remaining. It is concluded that the removal of the first two   waters from raffinose pentahydrate created defects, likely in the   form of vacancies, that provided the thermodynamic driving force   and disorder for subsequent conversion to the completely   amorphous state.

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