Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki, Japan.
Eur J Pharm Biopharm. 2010 Mar;74(3):461-6. doi: 10.1016/j.ejpb.2009.12.004. Epub 2009 Dec 14.
Size reduction of drug particles to the nanoscale is important in improving the dissolution rate of poorly water-soluble drugs. The aim of this study was to investigate the physicochemical properties of griseofulvin (GF)-lipid nanoparticles and the interactions between GF-lipid nanoparticles and various saccharides during freeze-drying. The phase transition temperature of the GF-lipid nanoparticle suspension was 56.8 degrees C, whereas that of the lipid nanoparticle suspension alone was 57.9 degrees C, indicating that the GF crystals were incorporated into the lipid phase. The mean particle size of a rehydrated suspension of xylose-containing freeze-dried GF-lipid nanoparticles was about 220 nm. However, the mean particle size on the rehydration of nanoparticles containing mannose (monosaccharide), fructose (disaccharide), lactose (disaccharide), or raffinose (trisaccharide) was about 60 nm, suggesting that these saccharides prevented aggregation during the freeze-drying process. Powder X-ray diffraction revealed that xylose existed in the crystalline state in the freeze-dried nanoparticles, whereas the other saccharides existed in amorphous states. Thus, the crystallization of the saccharide was found to be strongly correlated with the aggregation property of the nanoparticles. In the case of freeze-dried xylose, the nanoparticles were squeezed out as the saccharine crystal lattice arranged itself regularly. Then, the ejected nanoparticles were aggregated. In contrast, in the case of the other freeze-dried saccharide, the saccharide remained incorporated with the GF-lipid nanoparticles because its crystal lattice was arranged irregularly. Thus, the particle size was maintained.
将药物颗粒减小到纳米级对于提高难溶性药物的溶解速率非常重要。本研究旨在研究灰黄霉素（GF）-脂质纳米粒子的物理化学性质以及 GF-脂质纳米粒子与各种糖在冷冻干燥过程中的相互作用。GF-脂质纳米粒子悬浮液的相变温度为 56.8°C，而单独的脂质纳米粒子悬浮液的相变温度为 57.9°C，这表明 GF 晶体被掺入脂质相中。含有木糖的冷冻干燥 GF-脂质纳米粒子再水合悬浮液的平均粒径约为 220nm。然而，甘露糖（单糖）、果糖（二糖）、乳糖（二糖）或棉子糖（三糖）所含纳米粒子再水合的平均粒径约为 60nm，这表明这些糖在冷冻干燥过程中阻止了聚集。粉末 X 射线衍射表明，木糖以结晶态存在于冷冻干燥的纳米粒子中，而其他糖则以无定形态存在。因此，发现糖的结晶与纳米粒子的聚集性质密切相关。在冷冻干燥木糖的情况下，糖晶格排列规则，纳米粒子被挤出。然后，被挤出的纳米粒子聚集。相比之下，在其他冷冻干燥糖的情况下，由于其晶格排列不规则，糖仍然与 GF-脂质纳米粒子结合在一起，因此粒径得以保持。
