Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
Pharm Dev Technol. 2011 Jun;16(3):201-11. doi: 10.3109/10837450903584936. Epub 2010 Feb 9.
The purpose of this study was to gain a better understanding of which factors contribute to the eutectic composition of drug-polyethylene glycol (PEG) blends and to compare experimental values with predictions from the semi-empirical model developed by Lacoulonche et al. Eutectic compositions of various drug-PEG 3350 solid dispersions were predicted, assuming athermal mixing, and compared to experimentally determined eutectic points. The presence or absence of specific interactions between the drug and PEG 3350 were investigated using Fourier transform infrared (FT-IR) spectroscopy. The eutectic composition for haloperidol-PEG and loratadine-PEG solid dispersions was accurately predicted using the model, while predictions for aceclofenac-PEG and chlorpropamide-PEG were very different from those experimentally observed. Deviations in the model prediction from ideal behavior for the systems evaluated were confirmed to be due to the presence of specific interactions between the drug and polymer, as demonstrated by IR spectroscopy. Detailed analysis showed that the eutectic composition prediction from the model is interdependent on the crystal lattice energy of the drug compound (evaluated from the melting temperature and the heat of fusion) as well as the nature of the drug-polymer interactions. In conclusion, for compounds with melting points less than 200°C, the model is ideally suited for predicting the eutectic composition of systems where there is an absence of drug-polymer interactions.
本研究旨在深入了解哪些因素会影响药物-聚乙二醇（PEG）共混物的共晶组成，并将实验值与 Lacoulonche 等人开发的半经验模型的预测值进行比较。通过假设无热混合，预测了各种药物-PEG3350 固体分散体的共晶组成，并将其与实验测定的共晶点进行了比较。使用傅里叶变换红外（FT-IR）光谱法研究了药物和 PEG3350 之间是否存在特定相互作用。该模型准确预测了氟哌啶醇-PEG 和氯雷他定-PEG 固体分散体的共晶组成，而对醋氯芬酸-PEG 和氯丙酰胺-PEG 的预测与实验观察结果有很大差异。通过红外光谱证实，模型预测与理想行为的偏差是由于药物和聚合物之间存在特定相互作用所致。详细分析表明，模型对共晶组成的预测取决于药物化合物的晶格能（根据熔点和熔融热评估）以及药物-聚合物相互作用的性质。总之，对于熔点低于 200°C 的化合物，该模型非常适合预测不存在药物-聚合物相互作用的系统的共晶组成。
