Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Victoria 3052, Australia.
Eur J Pharm Sci. 2009 Nov 5;38(4):347-54. doi: 10.1016/j.ejps.2009.08.007. Epub 2009 Sep 2.
This study investigated the relationship between surface energy of micronized lactose, coarse lactose and salmeterol xinafoate and dispersibility from a mixture after storage at 75% RH. Surface energies, dispersibility, morphology, and the presence of amorphous domains were determined by inverse gas chromatography, twin stage impinger, scanning electron microscope and dynamic vapour sorption, respectively. The fine particle fraction of mixture decreased significantly in 4 weeks (P<0.05), reaching a static level in 3 months. Amorphous content was not detected in the micronized lactose, coarse lactose and salmeterol xinafoate. After conditioning stored samples at 75% RH for 2h, dispersive surface energy of both micronized and coarse lactose significantly decreased (P<0.05), while the polar surface energy of all significantly increased (P<0.05) resulting in significant increase in total surface energy after storage. After conditioning stored samples at 0% RH for 2h, no significant difference was observed in any surface energy parameter. This study concluded that the total surface energy increased during storage at high RH due to the adhered surface moisture. The mechanism of decreased dispersibility was related to increased capillary/solid bridging interactions and to possible increased interaction of contiguous particles due to increased polar surface energy.
本研究考察了在 75%相对湿度下储存后，微粉化乳糖、粗乳糖和沙美特罗昔萘酸盐的表面能与混合物的分散性之间的关系。通过反气相色谱、双级撞击器、扫描电子显微镜和动态蒸汽吸附分别测定了表面能、分散性、形态和无定形区域的存在。在 4 周内（P<0.05），混合物的细颗粒分数显著降低，3 个月后达到静态水平。在微粉化乳糖、粗乳糖和沙美特罗昔萘酸盐中均未检测到无定形含量。在 75%RH 下储存的样品经过 2 小时调节后，微粉化乳糖和粗乳糖的分散表面能显著降低（P<0.05），而所有样品的极性表面能均显著增加（P<0.05），导致储存后总表面能显著增加。在 0%RH 下储存的样品经过 2 小时调节后，任何表面能参数均无显著差异。本研究得出结论，由于附着的表面水分，高 RH 储存期间总表面能增加。分散性降低的机制与毛细管/固体桥接相互作用的增加以及由于极性表面能的增加而可能导致相邻颗粒相互作用的增加有关。
