Freeze Drying Focus Group (FDFG), Division of Pharmaceutics, D-91058 University of Erlangen, Erlangen, D-91058, Germany.
J Pharm Sci. 2013 Nov;102(11):4087-99. doi: 10.1002/jps.23723. Epub 2013 Sep 9.
Gas pycnometry is applied to determine the density of solid materials. The analysis of lyophilisates is particularly challenging because of their porous structure. In this study, the density of raw materials and freeze-dried products was determined using different pycnometric methodologies and gases [helium (He), nitrogen (N2 ), sulfur hexafluoride]. The number of purges was set to 60 independent of the gas used. Intact and ground lyophilisates were examined, and major differences were found between use of He and N2 . For example, the density of sucrose lyophilisates measured using He remained almost constant before (1.51 g/cm(3) ) and after (1.52 g/cm(3) ) grinding. In contrast, the density of a sucrose lyophilisate before grinding determined with N2 was 1.33 g/cm(3) . On the basis of μCT and scanning electron microscopy pictures, it appears likely that the majority of pores are interconnected, with only a small fraction of closed pores. Helium is able to penetrate deep into the freeze-dried matrix and is supposedly absorbed by the material. The N2 molecules were not able to penetrate closed pores; therefore, the skeletal density of an intact lyophilisate was determined. Reproducibility of the established method was verified, and freeze-dried orally disintegrating tablets of different compositions were analyzed.
气体比重瓶法用于测定固体材料的密度。由于其多孔结构，冻干物的分析特别具有挑战性。在这项研究中，使用不同的比重瓶方法和气体[氦（He）、氮（N2）、六氟化硫]来测定原材料和冻干产品的密度。无论使用哪种气体，吹扫次数都设置为 60 次。对完整和粉碎的冻干物进行了检查，发现 He 和 N2 的使用之间存在很大差异。例如，使用 He 测量的蔗糖冻干物的密度在粉碎前后几乎保持不变（1.51 g/cm(3)）。相比之下，用 N2 测定的未粉碎蔗糖冻干物的密度为 1.33 g/cm(3)。基于μCT 和扫描电子显微镜图片，似乎大多数孔是相互连通的，只有一小部分是封闭的。氦气能够深入冻干基质并被材料吸收。N2 分子无法穿透封闭的孔；因此，确定了完整冻干物的骨架密度。所建立方法的重现性得到了验证，并分析了不同组成的冻干口服崩解片。
