Taylor L S, York P
Postgraduate Studies in Pharmaceutical Technology, The School of Pharmacy, University of Bradford, West Yorkshire.
J Pharm Sci. 1998 Mar;87(3):347-55. doi: 10.1021/js970239m.
Many pharmaceutical compounds of interest form hydrates. The phase behavior of different particle size fractions of trehalose dihydrate was studied as the sugar was dehydrated by heating. Hot-stage microscopy, X-ray powder diffraction, thermogravimetric analysis, and differential scanning calorimetry were used to characterize the phase changes. Small particles (<45 microm) formed an amorphous phase on dehydration and subsequently liquefied at temperatures above the glass transition temperature of amorphous trehalose. Crystallization to the anhydrate was observed from this supercooled liquid. Large particles (>425 microm) underwent a solid-solid conversion from the dihydrate to the anhydrate at temperatures as low as 80 degrees C. This solid-solid conversion was explained by a catalytic effect of the liberated dihydrate water on the rearrangement of the dehydrated phase to the anhydrate. The large surface area-to-volume ratio of the small particles resulted in dehydration prior to attaining the threshold temperature for rearrangement, explaining why solid-solid conversion was absent for these particles.
许多具有研究价值的药物化合物会形成水合物。在通过加热使海藻糖二水合物脱水时，对其不同粒径部分的相行为进行了研究。利用热台显微镜、X射线粉末衍射、热重分析和差示扫描量热法来表征相变。小颗粒（<45微米）在脱水时形成非晶相，随后在高于非晶态海藻糖玻璃化转变温度的温度下液化。从这种过冷液体中观察到向无水物的结晶。大颗粒（>425微米）在低至80摄氏度的温度下经历了从二水合物到无水物的固-固转变。这种固-固转变被解释为释放出的二水合物水对脱水相重排为无水物的催化作用。小颗粒的大表面积与体积比导致在达到重排阈值温度之前就发生了脱水，这解释了为什么这些颗粒不存在固-固转变。
