Chatterjee Koustuv, Shalaev Evgenyi Y, Suryanarayanan Raj, Govindarajan Ramprakash
College of Pharmacy, 308, Harvard St. S.E., University of Minnesota, Minneapolis, MN 55455, USA.
J Pharm Sci. 2008 Jan;97(1):274-86. doi: 10.1002/jps.21081.
The goal was to evaluate the effects of acidity, expressed as the Hammett acidity function, on chemical reactivity in freeze-dried materials (lyophiles). Dextran-sucrose-citrate and polyvinyl pyrrolidone (PVP)-sucrose-citrate aqueous solutions, adjusted to pH values of 2.6, 2.8, and 3.0 were freeze dried, and characterized by X-ray powder diffractometry, DSC, isothermal microcalorimetry, and Karl Fischer titrimetry. Lyophiles were also prepared from identical solutions but containing bromophenol blue (BB). Diffuse reflectance-visible spectroscopy was used to measure the extent of BB protonation from which the Hammett acidity functions were determined. The stability studies were performed at 60 degrees C. All the freeze-dried samples were observed to be X-ray amorphous with <0.15% w/w water content. The T(g) of dextran lyophiles were approximately 20 degrees C higher than that of PVP lyophiles whereas enthalpy relaxation rates at 60 degrees C were similar. The Hammett acidity functions were significantly lower (i.e., higher acidity) for dextran systems (<2.2-2.6) when compared with PVP systems (3.3-3.9). The rate of sucrose inversion was significantly (an order of magnitude) higher in dextran lyophiles. This study showed that in amorphous matrices with comparable water content and structural relaxation times, chemical reactivity could be significantly different depending on the matrix "acidity".
目标是评估以哈米特酸度函数表示的酸度对冻干材料（冻干物）化学反应性的影响。将葡聚糖 - 蔗糖 - 柠檬酸盐和聚乙烯吡咯烷酮（PVP） - 蔗糖 - 柠檬酸盐水溶液调节至pH值2.6、2.8和3.0后进行冻干，并通过X射线粉末衍射、差示扫描量热法、等温微量热法和卡尔费休滴定法进行表征。还从相同但含有溴酚蓝（BB）的溶液中制备冻干物。使用漫反射可见光谱法测量BB的质子化程度，由此确定哈米特酸度函数。稳定性研究在60℃下进行。观察到所有冻干样品均为X射线非晶态，水含量<0.15%（w/w）。葡聚糖冻干物的玻璃化转变温度（Tg）比PVP冻干物高约20℃，而60℃下的焓松弛速率相似。与PVP体系（3.3 - 3.9）相比，葡聚糖体系的哈米特酸度函数显著更低（即酸度更高）（<2.2 - 2.6）。葡聚糖冻干物中蔗糖转化的速率显著更高（一个数量级）。这项研究表明，在具有可比水含量和结构弛豫时间的无定形基质中，化学反应性可能因基质“酸度”而有显著差异。
