Morris K R, Knipp G T, Serajuddin A T
Pharmaceutics R&D Department, Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, NJ 08903.
J Pharm Sci. 1992 Dec;81(12):1185-8. doi: 10.1002/jps.2600811212.
The structural properties of the mixtures of polysorbate 80 with various polyethylene glycols (PEG), viz., PEG 1000, PEG 1450, PEG 3350, and PEG 8000, have been investigated by powder X-ray diffraction (XRD) and differential scanning calorimetric studies. These mixtures may be used as solid dispersion vehicles to insure complete dissolution of poorly water-soluble drugs. Although polysorbate 80 is a liquid at room temperature, the PEG-polysorbate 80 mixtures with up to 75% (w/w) polysorbate 80 were solid. The XRD studies revealed that the crystal structures (d-spacings) of the PEGs (M(r) 1000, 1450, 3350, and 8000) did not change with increasing amounts of polysorbate 80 in the mixture. The intensities of the XRD peaks, however, varied approximately in proportion to the concentration of PEG present. Similarly, the differential scanning calorimetric studies showed that the melting behavior of a PEG-polysorbate 80 mixture was similar to that of the PEG used. The lowering of the mp of a particular PEG due to the presence of 50% (w/w) polysorbate 80 in the mixture was < 6 degrees C, and the decrease in mp was < 12 degrees C in the presence of 75% (w/w) polysorbate 80. When enthalpies of fusion of the mixtures were normalized for the amounts of PEGs present, they were similar to those of pure PEGs. These results indicate that the crystalline structure of PEG in a PEG-polysorbate 80 mixture is substantially the same as that of the pure PEG, and that polysorbate 80 is incorporated into the amorphous region of PEG solid structure.
通过粉末X射线衍射（XRD）和差示扫描量热研究，对聚山梨酯80与各种聚乙二醇（PEG），即PEG 1000、PEG 1450、PEG 3350和PEG 8000的混合物的结构性质进行了研究。这些混合物可用作固体分散载体，以确保难溶性药物完全溶解。尽管聚山梨酯80在室温下是液体，但聚山梨酯80含量高达75%（w/w）的PEG - 聚山梨酯80混合物却是固体。XRD研究表明，PEG（分子量1000、1450、3350和8000）的晶体结构（d间距）不会随着混合物中聚山梨酯80含量的增加而改变。然而，XRD峰的强度大致与存在的PEG浓度成比例变化。同样，差示扫描量热研究表明，PEG - 聚山梨酯80混合物的熔化行为与所用PEG的相似。由于混合物中存在50%（w/w）的聚山梨酯80，特定PEG的熔点降低<6℃，在存在75%（w/w）聚山梨酯80的情况下，熔点降低<12℃。当将混合物的熔化焓根据存在的PEG量进行归一化时，它们与纯PEG的相似。这些结果表明，PEG - 聚山梨酯80混合物中PEG的晶体结构与纯PEG的基本相同，并且聚山梨酯80被纳入PEG固体结构的非晶区。
