Takeuchi H, Yasuji T, Yamamoto H, Kawashima Y
Gifu Pharmaceutical University, Japan.
Pharm Dev Technol. 2000;5(3):355-63. doi: 10.1081/pdt-100100551.
The purpose of this study was to investigate the temperature- and moisture-induced crystallization of amorphous lactose in the composite particles prepared by spray-drying an aqueous solution of crystalline lactose and sodium alginate. The temperature-induced crystallization of amorphous lactose in the composite particles was suppressed by increasing the amount of sodium alginate in the particles. The stabilizing effect of sodium alginate on amorphous lactose in the composite particles was greater than that in physical mixtures having the same formulating ratios. The improved stability of amorphous lactose in the composite particles was attributed to an increase in the glass transition temperature (Tg) of the mixture. Moisture-induced crystallization of amorphous lactose was also retarded by increasing the amount of sodium alginate in composite particles. Although the Tg of the mixture was reduced by increasing the water content of the particles, the values were higher than that of 100% amorphous lactose when particles of the same water content were compared. The change in the Tg of the composite particles with increasing water content was interpreted as involving three components of the Gordon-Taylor equation. In the amorphous lactose-sodium alginate systems, the Tg values of the composite particles containing sodium alginate were higher than the theoretical line predicted by two components of the Gordon-Taylor equation. These results suggested that there was a specific interaction between the sodium alginate and lactose molecules. This specific interaction was suggested by the fact that only very little amorphous lactose was measured in the spray-dried composite particles stored under humid conditions using differential scanning calorimetry. This molecular interaction may also be partly responsible for the suppression of both the temperature- and moisture-induced crystallization of amorphous lactose in the composite particles.
本研究的目的是调查通过喷雾干燥结晶乳糖和海藻酸钠的水溶液制备的复合颗粒中，无定形乳糖的温度和湿度诱导结晶情况。通过增加颗粒中海藻酸钠的量，可以抑制复合颗粒中无定形乳糖的温度诱导结晶。海藻酸钠对复合颗粒中无定形乳糖的稳定作用大于具有相同配方比例的物理混合物中的稳定作用。复合颗粒中无定形乳糖稳定性的提高归因于混合物玻璃化转变温度（Tg）的升高。增加复合颗粒中海藻酸钠的量也会延缓无定形乳糖的湿度诱导结晶。尽管通过增加颗粒中的含水量会降低混合物的Tg，但当比较相同含水量的颗粒时，其值高于100%无定形乳糖的Tg值。复合颗粒的Tg随含水量增加的变化被解释为涉及戈登-泰勒方程的三个组分。在无定形乳糖-海藻酸钠体系中，含有海藻酸钠的复合颗粒的Tg值高于戈登-泰勒方程两个组分预测的理论线。这些结果表明海藻酸钠和乳糖分子之间存在特定的相互作用。使用差示扫描量热法在潮湿条件下储存的喷雾干燥复合颗粒中仅测量到极少的无定形乳糖这一事实表明了这种特定的相互作用。这种分子相互作用也可能部分负责抑制复合颗粒中无定形乳糖的温度和湿度诱导结晶。
